Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury.

Of course this is in mice so your doctor will never take a chance on giving it to you post-stroke.
This from 2011 tested xenon gas for heart patients.

xenon gas and stroke rehab

Whom is going to run a clinical test in humans?  Possible use for concussions?

The mouse test here:

 Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury.

Campos-Pires, Rita MD; Armstrong, Scott P. PhD; Sebastiani, Anne MD; Luh, Clara PhD; Gruss, Marco MD; Radyushkin, Konstantin MD; Hirnet, Tobias; Werner, Christian MD, PhD; Engelhard, Kristin MD, PhD; Franks, Nicholas P. PhD; Thal, Serge C. MD; Dickinson, Robert PhD

Published Ahead-of-Print

Abstract

Objectives: To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window.

Design: Controlled animal study.

Setting: University research laboratory.

Subjects: Male C57BL/6N mice (n = 196).

Interventions: Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact.

Measurements and Main Results: Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma.

Conclusions: These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.

‘Ecstasy’ as a social drug: MDMA preferentially affects responses to emotional stimuli with social content

Would ecstasy help survivors be better at social engagement post-stroke? Since social engagement is a needed construct for better recovery.  Ask your doctor, do not self medicate.

The latest here:

‘Ecstasy’ as a social drug: MDMA preferentially affects responses to emotional stimuli with social content

1. Margaret C. Wardle,
2. Matthew G. Kirkpatrick and
3. Harriet de Wit

+ Author Affiliations

1. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA

1. Correspondence should be addressed to Harriet de Wit, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841S. Maryland Ave., MC3077, Chicago, IL 60637, USA. E-mail: hdew@uchicago.edu

• Received November 6, 2013.
• Revision received February 7, 2014.
• Accepted February 10, 2014.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is used recreationally to improve mood and sociability, and has generated clinical interest as a possible adjunct to psychotherapy. One way that MDMA may produce positive ‘prosocial’ effects is by changing responses to emotional stimuli, especially stimuli with social content. Here, we examined for the first time how MDMA affects subjective responses to positive, negative and neutral emotional pictures with and without social content. We hypothesized that MDMA would dose-dependently increase reactivity to positive emotional stimuli and dampen reactivity to negative stimuli, and that these effects would be most pronounced for pictures with people in them. The data were obtained from two studies using similar designs with healthy occasional MDMA users (total N = 101). During each session, participants received MDMA (0, 0.75 and 1.5 mg/kg oral), and then rated their positive and negative responses to standardized positive, negative and neutral pictures with and without social content. MDMA increased positive ratings of positive social pictures, but reduced positive ratings of non-social positive pictures. We speculate this ‘socially selective’ effect contributes to the prosocial effects of MDMA by increasing the comparative value of social contact and closeness with others. This effect may also contribute to its attractiveness to recreational users.

Coping with Stress – Some Essential Constructs

From the uberBrain.  You probably have to teach your doctor about the stress of recovering from a stroke.  PTSD following stroke or TIA was 23%.
A 1 hour talk.
Gadadhara Pandi, an author, meditation teacher, inspirational speaker, and lecturer at Columbia University gave a talk organized by Google . Pandi talks about stress management for work-life balance – something we could probably all stand to be a little better at.
http://www.uberbrain.net/2014/coping-with-stress-essential-constructs/

Lake Michigan beach walking

This was both great and depressing. Great because in the really loose sand I can now walk barefoot without turning my ankle. We did walk 1/2 mile down the beach on packed sand and then watched the waves from beach chairs for an extended period. Depressing because looking at the 2-3 foot waves rolling in and I can't get in my sea kayak and paddle thru them to the calmer waters further out. It was an 1.5 hour drive to get to a friends house  in Saugatuck, after the beach we visited art galleries and drank wine.

Maggots make a comeback as a cheap, non-antibiotic treatment for infected wounds

So ask your doctor if your dead area in your brain needs cleaning out by maggots and using trepanation to get there.
http://medcitynews.com/2014/09/maggots-make-comeback-cheap-non-antibiotic-treatment-infected-wounds/?

Cross country running

I work on the Michigan State University campus and last night when leaving dozens of men were running cross country on one of the farms on campus. It was damned depressing watching them effortlessly run. I used to be able to do that and someday will again.

29 Signs You Ran Cross-Country In High School

 

 

Lack of sleep may shrink your brain

I slept like shit in the hospital so I was given sleeping pills. Is your doctor concerned about not letting your brain shrink while you recover from your stroke? What is your doctors stroke protocol to prevent such shrinkage?

Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults

1. Claire E. Sexton, DPhil,
2. Andreas B. Storsve, MSc,
3. Kristine B. Walhovd, PhD,
4. Heidi Johansen-Berg, DPhil and
5. Anders M. Fjell, PhD

+Show Affiliations

| + Show Full Disclosures

1. Correspondence to Dr. Sexton: claire.sexton@ndcn.ox.ac.uk

1. Published online before print September 3, 2014, doi: 10.1212/WNL.0000000000000774 Neurology 10.1212/WNL.0000000000000774

• Abstract
• Full Text (PDF)

Abstract

Objective: To examine the relationship between sleep quality and cortical and hippocampal volume and atrophy within a community-based sample, explore the influence of age on results, and assess the possible confounding effects of physical activity levels, body mass index (BMI), and blood pressure.

Methods: In 147 community-dwelling adults (92 female; age 53.9 ± 15.5 years), sleep quality was measured using the Pittsburgh Sleep Quality Index and correlated with cross-sectional measures of volume and longitudinal measures of atrophy derived from MRI scans separated by an average of 3.5 years. Exploratory post hoc analysis compared correlations between different age groups and included physical activity, BMI, and blood pressure as additional covariates.

Results: Poor sleep quality was associated with reduced volume within the right superior frontal cortex in cross-sectional analyses, and an increased rate of atrophy within widespread frontal, temporal, and parietal regions in longitudinal analyses. Results were largely driven by correlations within adults over the age of 60, and could not be explained by variation in physical activity, BMI, or blood pressure. Sleep quality was not associated with hippocampal volume or atrophy.

Conclusions: We found that longitudinal measures of cortical atrophy were widely correlated with sleep quality. Poor sleep quality may be a cause or a consequence of brain atrophy, and future studies examining the effect of interventions that improve sleep quality on rates of atrophy may hold key insights into the direction of this relationship

 

Trials begin with a new fall detector for the elderly that automatically notifies the emergency services

Maybe something for peace of mind for your caregiver.
But maybe there are already apps out there that do the same thing.

Seniors Using iPhone Apps to Alert When They Fall

The latest here:

Trials begin with a new fall detector for the elderly that automatically notifies the emergency services

Researchers from the Technical Research Centre for Dependency Care and Autonomous Living (CETpD), on the UPC’s Vilanova i la Geltrú Campus, have designed a device that detects falls in elderly people without them having to press a button for assistance. It pinpoints their location inside or outside the home and notifies the emergency services if necessary.
The Universitat Politècnica de Catalunya · BarcelonaTech (UPC) leads the consortium behind the European project Fall Detector for the Elderly (FATE), which also includes TicSalut, 061 CatSalut Respon, Hospital Clínic and EAP Sardenya. The fall detector, which is currently being trialled, brings greater safety both inside and outside the home.
The FATE system consists of a small, highly sensitive fall detector fitted into a belt that users wear throughout the day. The device’s sensors detect movements consistent with a fall and integrated wireless technology locates the user’s position, inside or outside the home.
The system also includes a bed presence sensor that detects prolonged absences during the night and triggers an alarm if the user does not return to bed within a stipulated period. The aim is to minimise the effects of an accident on fragile patients who may not be physically capable of calling for help if they suffer a fall.
The technology for the FATE device was developed by researchers at the Technical Research Centre for Dependency Care and Autonomous Living (CETpD) on the UPC’s Vilanova i la Geltrú Campus, under the direction of Joan Cabestany.
Direct contact with emergency services
When the FATE device detects that a user has suffered a fall, it sends an automatic notification to the Catalan ambulance service, 061 CatSalut Respon, which locates the patient and contacts them to establish the details of the accident. The situation can then be assessed by the CatSalut Respon medical team, who provide guidance on how best to deal with the situation and send an SEM ambulance if further medical assistance is required.
The FATE protocol greatly improves patient safety, primarily for those who live alone, as it provides the security of automatic medical attention in the event of a fall.
FATE trialled in elderly patients
Patients selected for the trial by the project team in Catalonia were taken from the primary care group at EAP Sardenya and Hospital Clínic in Barcelona.
The study is divided into two six-month periods: during the first, half of the patients wear the device and the other half serve as a control group; during the second, the groups are reversed.
Over the course of the study patients are visited on a monthly basis and contacted by telephone each week to evaluate their general state of health and to discuss any problems with the device.
The European project is coordinated by the UPC and carried out by a consortium that also includes partners in Ireland and Italy. The study population for the pilot phase comprises 50 patients in Ireland, 80 in Italy and 75 in Catalonia and was selected according to the relative risk of suffering an accidental fall or a fall caused by an existing medical condition.
Falls are a serious problem in the elderly population, estimated to affect 30% of over-65s and often causing severe physical restrictions. The worst effects are generally observed in those living alone who, in the event of a fall, may be unable to move and can spend considerable periods of time on the ground before they receive medical assistance. The delay in treatment can lead to irreversible health problems.
Immediate detection enables an immediate response from the 061 emergency services, ensuring that the necessary medical assistance is provided as swiftly as possible.
The FATE project began in 2012 and is scheduled to run for 39 months. The pilot phase started at the beginning of 2014 and will continue into 2015.

Stroke Rounds: Potassium Tied to Lower Stroke Risk

Silly and lazy research. They could have looked up old research that showed this possible link years ago. My god, is everyone stupid in the stroke world?

Effect of high potassium diet on endothelial function  June 2014

Slash Risk of Stroke with More Potassium and Less Salt  June 2013

Why eat three bananas a day?    April 2012

And the latest here:

Stroke Rounds: Potassium Tied to Lower Stroke Risk

 

 

Low-Budget Stroke Campaign Makes High Impact at VCU - Whoopee! another press release campaign

I absolutely hate the laziness of these press release campaigns. It looks like they are doing something useful but by doing this they are not solving any of the major problems in stroke. They are all just kicking the f*cking can down the road.
http://www.healthleadersmedia.com/content/MAR-308022/LowBudget-Stroke-Campaign-Makes-High-Impact-at-VCU

Measures of gait stability: performance on adults and toddlers at the beginning of independent walking

I would think that your doctor and therapist should be objectively evaluating your gait stability prior to discharge. 
http://www.jneuroengrehab.com/content/11/1/131/abstract

Maria Cristina Bisi, Federico Riva and Rita Stagni

• 
  

Author Affiliations

For all author emails, please log on.

Journal of NeuroEngineering and Rehabilitation 2014, 11:131  doi:10.1186/1743-0003-11-131
Published: 3 September 2014

Abstract (provisional)

Background

Quantifying gait stability is a topic of high relevance and a number of possible measures have been proposed. The problem in validating these methods is the necessity to identify a-priori unstable individuals. Since proposed methods do not make any assumption on the characteristics of the subjects, the aim of the present study was to test the performance of gait stability measures on individuals whose gait is a-priori assumed unstable: toddlers at the onset of independent walking.

Methods

Ten toddlers, ten adults and ten elderly subjects were included in the study. Data from toddlers were acquired longitudinally over a 6-month period to test if the methods detected the increase in gait stability with experience, and if they could differentiate between toddlers and young adults. Data from elderly subjects were expected to indicate a stability value in between the other two groups. Accelerations and angular velocities of the trunk and of the leg were measured using two tri-axial inertial sensors. The following methods for quantifying gait stability were applied: stride time variability, Poincare plots, harmonic ratio, short term Lyapunov exponents, maximum Floquet multipliers, recurrence quantification analysis and multiscale entropy. An unpaired t-test (level of significance of 5%) was performed on the toddlers and the young adults groups for each method and, for toddlers, for each evaluated stage of gait development.

Results

Methods for discerning between the toddler and the adult groups were: stride time variability, Poincare plots, harmonic ratio, short term Lyapunov exponents (state space composed by the three linear acceleration of the trunk), recurrence quantification analysis and multiscale entropy (when applied on the vertical or on the antero-posterior L5 accelerations).

Conclusions

Results suggested that harmonic ratio and recurrence quantification analysis (What's this?) better discern gait stability in the analyzed subjects, differentiating not only between unstable toddlers and stable healthy adults but also evidencing the expected trend of the toddlers towards a higher stability with walking experience, and indicating elderly subjects as stable as or less stable than young adults.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

My Chablis wine review for the NYTimes

Eric Asimov does a monthly column where he suggests a wine style and asks readers to write in their comments.

Your Next Lesson: Chablis

My writeup:
  Because this month was a white wine we didn't have the standard argument over whether the wine was wine-colored enough. The flavor was agreed to be wine, although we did get pear and mango suggestions, and someone throwing in grapefruit.  Our Stalinistic leader tried to  enforce the no red wine rule for extra bottles being brought in. A revolution was started anyway with a bottle of red and two bottles of Ratafia  Our host brought 4 bottles, the rest of the crew brought 7 bottles. Our best was 14 bottles the night we did beaujolais. Anything for an excuse to get together and drink wine.

The food was our standard potluck; appetizers, veggie dishes and pies. The quiche was wonderful.
 The outdoor deck was wonderful with fireflies entertaining us at dusk. A few tried looking for glowworms in the grass but were unsuccessful due to the inability to get down low enough without toppling.
  One participant tried to impress us with this description of the first bottle. It was flowery with a triangular aftertaste that lazered the taste buds with the creaminess of  peach melba although it still was not intellectually satisfying. I came back with, it was band-aid colored and flavored and not Teenage  Mutant Ninja Turtle ones.The box Chablis wine from 2011 was smelled and dumped. Even our non-discriminating tastes were offended. All in all a very good evening of wine food and friends.

Isabelle Allende: How to live passionately—no matter your age

I would also say no matter your disability also. 

Isabelle Allende: How to live passionately—no matter your age 

This leads directly into this Ani DeFranco song.

If you’re not getting happier as you get older Then you’re fuckin’ up

Or maybe you would rather listen to this TEDx talk;

Older people are happier

 

Does Alcohol Kill Brain Cells?

No, but it does make it harder for messages to cross the synapses. Sounds like a great protocol to speed up your recovery because you always have to do things the hard way to get to a faster recovery. I should be fully recovered by all the alcohol I've been drinking to facilitate my social integration here in Michigan. Don't follow my ideas like bar stool rehab. It is definitely safer than my chainsaw rehab. I can do this because I take no other medicine and I have no doctor to tell me otherwise.
https://richarddawkins.net/2014/08/does-alcohol-kill-brain-cells/
A quick 2 minute explanation.

Brain regeneration: Crayfish turn blood into neurons

Fascinating idea. Whom is going to research this to see if this could be translated to humans? A great stroke association would create an RFP for researchers to respond to with how they would solve the problem and the cost for that.
http://www.newscientist.com/article/dn26042-brain-regeneration-crayfish-turn-blood-into-neurons.html#.VAYaTGOVCug

Think crayfish and you probably think supper, perhaps with mayo on the side. You probably don't think of their brains. Admittedly, crayfish aren't known for their grey matter, but that might be about to change: they can grow new brain cells from blood.

Humans can make new neurons, but only from specialised stem cells. Crayfish, meanwhile, can convert blood to neurons that resupply their eyestalks and smell circuits. Although it's a long way from crayfish to humans, the discovery may one day help us to regenerate our own brain cells.

More at link.

100 Most Influential People in Healthcare - 2014

Not a single person associated with stroke, dementia or Alzheimers is on the list. These really aren't the thought leaders, these are the CEOs of large health care companies. And that great stroke association would be contacting every single one of them to let them know of their  

1 in 4 per WHO that has a stroke

 and the fact that your chances of recovering is only 10%. That might light a fire under the medical world. Everything in stroke is a failure and that needs to be publicized.
http://www.modernhealthcare.com/section/100-Most-Influential-2014

How many hours of therapy do you need to do to recover from a stroke?

Malcolm Gladwell's highly popular book, Outliers, estimates 10,000 hours as the time it takes to become a high-level athlete or musician.
First you would need to accurately know how many muscles were affected by your stroke, split between just damaged in the penumbra and the dead ones. I'm sure your neurologist has no f*cking clue as to the answer to that question.
The damaged ones are the only ones counted here

A (slightly tongue-in-cheek) tally of the body’s many muscles

The grand total

Well, this is how I calculate it. We have …

• 200 muscles that might get discussed in a gym
• 100 more muscles that are pretty obscure, but any self-respecting massage therapist still knows about them
• 400 more muscles that are really danged obscure, but various specialists know about them, and a handful of them are of special interest
• several million hair-raising muscles
• several billion smooth muscles cells blended together
• exactly 1 heart muscle

So I’m going to go with a grand total of approximately 50,100,000,701 muscles, accurate to within 99%.
--------------------------------------------------------------------------------------------------------------------
Let's say you blew out all of your motor cortex on one side and taking the first three bullets that would mean 350 muscles needing retraining.
I'll make it simple and assume that there is one specific exercise for each muscle, Think of body builders and what they do to get that definition.
350 * 10,000 = 3.5 million hours needed to totally recover.
24 hours a day * 365 days = 8760 hours in a year
If you worked constantly all year you might be able to recover one muscle
3.5m/8760 = 399.54 years before you are completely recovered and you are not going to be able to ever sleep again. Lots of Red Bulls for you.
And do you really think your therapist has stroke protocols for each voluntary muscle in the body?

This is why the rehabilitation silo as currently set up is not where the solution to stroke recovery is. The solution is preventing neuronal death in the first week. Then rehabilitation might have a chance to get people to recovery. 

I look forward to therapists and neurologists around the world telling me exactly why I'm wrong and providing exact calculations for recovery.  That'll be the day, by Buddy Holly.

Reciprocal Inhibition

Thanks to Amy for finding this for me . This was me trying to understand how muscles are told to relax. My OT used to command me to relax my spastic muscles, it never worked. Somebody out there has to be brilliant enough that they can write up a stroke protocol to fix the fucking spasticity. And since that won't occur for 50 years you had better start figuring out how to treat spasticity on your own. You're screwed until then.

Reciprocal Inhibition

NOMI - Nitric oxide inhalation in heart attack patients sends mixed messages, but may offer benefit.

Nitric Oxide seems useful for stroke according to these research points. Whom is going to make a definitive statement about how and when NO is used in stroke? Anyone at all? Or are we just going to wait for somebody else to solve this problem?

Modulation of Adult Neurogenesis by the Nitric Oxide System

Efficacy of Nitric Oxide in Stroke' (ENOS) study 

Inhaled Nitric Oxide Protects Males But not Females from Neonatal Mouse Hypoxia–Ischemia Brain Injury 

 

  Inhaled Nitric Oxide Protects Males But not Females from Neonatal Mouse Hypoxia–Ischemia Brain Injury

 

  Regulation of Injury-Induced Neurogenesis by Nitric Oxide

 

 Nitric Oxide and the Biological Cascades Underlying Increased Neurogenesis, Enhanced Learning Ability, and Academic Ability as an Effect of Increased Bouts of Physical Activity

  Inhalation of nitric oxide could help improve blood flow to ischemic brain

  Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function

 

  Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke

 

Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function

 And here is the heart benefit.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=144932&CultureCode=en
Inhaled nitric oxide, delivered to heart attack patients before and during treatment with percutaneous coronary intervention (PCI) did not reduce the extent of damaged tissue (infarct), but may have improved recovery, according to Hot Line results presented today at ESC Congress 2014.
The NOMI (Nitric Oxide for inhalation to reduce reperfusion injury in acute st-elevation Myocardial Infarction) trial was based on the hypothesis that nitric oxide inhalation can reduce the injury caused to heart tissue during reperfusion (restoration of blood flow when a blocked artery is re-opened), according to Stefan Janssens, MD, PhD from University Hospital Gasthuisberg of Leuven, Belgium.
The trial included 250 heart attack patients with ST elevation myocardial infarction (STEMI) who presented between two and 12 hours after symptom onset.
Patients were randomised to receive supplemental oxygen via face mask, with (n=125) or without (n=125) nitric oxide at a concentration of 80 parts per million.
The gas was started in the catheterization laboratory prior to PCI and continued up to 4 hours after the start of reperfusion.
Magnetic resonance imaging (MRI) was used to measure infarct size, assessed as a fraction of left ventricular (LV) mass, as well as to evaluate LV remodeling (injury-related changes).
The study found that between 48-72 hours after the procedure there were no differences in infarct size between patients who received nitric oxide and those who did not (18% vs 19.4%, P=0.44).
However, a pre-specified sub-group analysis of patients who had received intracoronary or intravenous nitroglycerin (IC/IV NTG) – the administration of which was left to the discretion of the local investigators- showed a significant interaction  (P=0.014) with the use of inhaled nitric oxide. Among NTG-naïve patients (n=132), nitric oxide inhalation was associated with significantly smaller infarcts compared to patients who had previously received NTG (n=93).
In the total population, MRI at 48-72 hours showed a trend for improved LV functional recovery with nitric oxide, which became significant at 4 months (P=0.048).
Functional recovery was significantly better with nitric oxide in the sub-group of NTG-naïve patients.
Nitric oxide did not cause major adverse events, and for a secondary composite endpoint of death, recurrent ischemia, stroke or rehospitalisations it was associated with a trend towards a lower event rate (P=0.10).
The NOMI trial is the first to investigate the impact of nitric oxide inhalation on myocardial reperfusion injury, infarct size, and cardiac recovery, said Professor Janssens.
“While it did not show a significant reduction in infarct size in the overall study population, the findings suggest that nitric oxide inhalation merits further investigation in STEMI patients,” he concluded.

Don't Let the Stroke Win - NSA email

This email from the National Stroke Association is why stroke is winning. Talking prevention is lazy when you could actually spend a little money and intellectual capital and actually solve the major problems in stroke. But no, you decide to keep doing the same things that doesn't address anything for survivors. 
Waiting for someone else to solve the damn stroke problem?
The board of directors must not be paying any attention to what the NSA is doing.
http://www.stroke.org/site/MessageViewer?dlv_id=36021&em_id=25941.0

Ebselen, an anti-inflammatory antioxidant

A great stroke association would finish off clinical testing of this to see if this would be useful for survivors. No one else is going to do it.
From this article;

The limits of lithium, and the hunt for a better alternative

 Ebselen, an anti-inflammatory antioxidant, was originally developed by Daiichi Sankyo, in Japan, to treat patients who had suffered a stroke. But the compound was never marketed and has since come off patent. It’s also part of the National Institutes of Health Clinical Collection—several hundred small molecules that have, to some extent, gone through the gamut of human clinical trials and have been found to be safe, but never reached final FDA approval.

Does functional MRI detect activation in white matter? A review of emerging evidence, issues, and future directions

Right now your doctor has no clue as to how much damage is in your white matter. With no diagnosis of damage there can be no idea of what stroke protocols work in correcting such damage. You doctor is totally flying blind when trying to determine what needs to be done. But then that is no different that what occurs today in any therapy given to help survivors recover. Everything in stroke is flying blind, no wonder only 10% fully recover. Would you want a blind doctor operating on clipping your aneurysm in your brain? 

http://journal.frontiersin.org/Journal/10.3389/fnins.2014.00239/full? 

Jodie R. Gawryluk^1†, Erin L. Mazerolle^2† and Ryan C. N. D'Arcy^3,4*

• ¹Division of Medical Sciences, Department of Psychology, University of Victoria, Victoria, BC, Canada
• ²Department of Radiology, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
• ³Applied Sciences, Simon Fraser University, Burnaby, BC, Canada
• ⁴Fraser Health Authority, Surrey Memorial Hospital, Surrey, BC, Canada

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of activated brain regions. Until recently, fMRI studies have focused on gray matter. There are two main reasons white matter fMRI remains controversial: (1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in white matter than gray matter and (2) fMRI signal has been associated with post-synaptic potentials (mainly localized in gray matter) as opposed to action potentials (the primary type of neural activity in white matter). Despite these observations, there is no direct evidence against measuring fMRI activation in white matter and reports of fMRI activation in white matter continue to increase. The questions underlying white matter fMRI activation are important. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. The current review provides an overview of the motivation to investigate white matter fMRI activation, as well as the published evidence of this phenomenon. We speculate on possible neurophysiologic bases of white matter fMRI signals, and discuss potential explanations for why reports of white matter fMRI activation are relatively scarce. We end with a discussion of future basic and clinical research directions in the study of white matter fMRI.

Motivation to Investigate White Matter fMRI

Functional magnetic resonance imaging (fMRI) is used to visualize the neuroanatomical regions associated with brain function. The most commonly used technique for fMRI, blood oxygenation level dependent (BOLD) contrast, was first demonstrated in the early 1990s (Ogawa et al., 1992). Since then, fMRI has broadened our understanding of how the brain functions under both healthy and diseased conditions (e.g., Rosen et al., 1998; Dolan, 2008; Haller and Bartsch, 2009; Rosen and Savoy, 2012). Although fMRI continues to grow in popularity in both research and clinical settings, the full potential of this technique remains untapped because fMRI activity has historically not been considered to be detectable in white matter tissue (Logothetis and Wandell, 2004). In spite of this, fMRI studies often produce activation in white matter and consequently there has been much debate over whether this activation is a true or false representation of underlying neural activity. There are two main reasons that white matter fMRI is controversial. First, BOLD signal relies on cerebral blood volume and flow, which are three to seven times lower in white matter (Rostrup et al., 2000; Preibisch and Haase, 2001; Helenius et al., 2003). However, the vasculature and perfusion of white matter (Figure 1) are capable of supporting hemodynamic changes that are detectable with BOLD fMRI [see Section White Matter Vasculature, Cerebral Blood Flow (CBF), and Cerebral Blood Volume (CBV)]. Second, the primary source of fMRI signal is thought to arise from post-synaptic potentials (which occur mainly in gray matter) as opposed to action potentials (e.g., Logothetis et al., 2001; but see e.g., Smith et al., 2002). However, neither of these statements exclude the possibility, and there is no direct evidence against the possibility of measuring fMRI activation in white matter.

More at link.

Lipid dynamics at dendritic spines

We probably need dendritic branching to recover. What is your incompetent? doctor doing to accomplish that? Look at the last bolded sentence, this is what makes me think cholesterol reduction is not necessarily good for our recovery. But I'm stupid because I'm not medically trained and thus should never be listened to. Ask your doctor if statins reduce the cholesterol in the brain.

Lipid dynamics at dendritic spines

Carlos Gerardo Dotti^*, Jose Antonio Esteban and María Dolores Ledesma^*

• Centro Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain

Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

Introduction

At most excitatory synapses in the Central Nervous System, presynaptic boutons synapse onto small membrane protrusions that emerge from the dendritic shaft: the dendritic spines. Changes in dendritic spine number, size and shape contribute to determine the strength of excitatory synaptic transmission (Yuste and Bonhoeffer, 2001; Carlisle and Kennedy, 2005). The remodeling of these membrane protrusions in response to stimuli depends on lipids, which are major components of the membrane with the ability to shape it and modify protein activities within. However, only recently the contribution of spine lipids has attracted similar attention to that of spine proteins. Pioneer work showing the requirement of glial cholesterol for synapse formation (Mauch et al., 2001) and the elimination of spines upon reduction of cholesterol or sphingolipids (Hering et al., 2003) triggered research in this field. Technical progress facilitates today the not so long ago impossible analysis of the subtle changes in lipid composition and of the topographical distribution of individual lipid species in cellular compartments. Probes have been developed to label lipid molecules such as new generation fluorescent tags (Eggeling et al., 2009) or modified toxins with specific lipid binding abilities such as the theta-toxin or lysenin, which bind cholesterol or sphingomyelin, respectively (Abe et al., 2012). These probes together with advanced microscopy techniques that achieve sub-diffraction optical resolution (i.e., near-field scanning optical microscopy (NSOM), photoactivated localization microscopy (PALM) stochastic optical reconstruction microscopy (STORM) or stimulated depletion (STED) fluorescent microscopy) allow the direct observation of the nanoscale dynamics of membrane lipids in a living cell (Eggeling et al., 2009; van Zanten et al., 2010; Castro et al., 2013). As we gain insight on how lipids and their metabolic enzymes regulate dendritic spine shape and protein function their importance is confirmed and strengthened. We aim here to review this knowledge focusing the attention on the dynamic lipidomics of dendritic spines. We will also discuss about how this influences synaptic plasticity through the modulation of glutamate receptors of the AMPA and NMDA-type (AMPARc and NMDARc). These receptors are instrumental to elicit Long Term Potentiation (LTP) and Long Term Depression (LTD), which are considered the molecular mechanisms underlying learning and memory (Neves et al., 2008; Collingridge et al., 2010).

Lipid Composition at Dendritic Spines

A relevant question about spine physiology is whether spine membrane lipid composition and organization is different to that of the dendritic shaft membranes from which these protrusions emerge. A systematic analysis of spine lipid composition is lacking due to technical limitations. However, accumulating evidence indicates it differs from that of the shaft. This raises questions such as why this specificity is necessary and how it is achieved, maintained or modulated upon stimuli. Until now, most of the information on synaptic lipid composition comes from the biochemical analysis of synaptosomal preparations. Functional studies have also highlighted the relevant contribution of certain lipids to spine physiology. From these two types of approaches we now know that cholesterol and sphingolipids are enriched in spines. Because of their chemical affinity these lipids form highly dynamic and heterogeneous membrane nanodomains, the so called rafts, which can be stabilized to form larger platforms by protein-protein or protein-lipid interactions (Pike, 2006). Rafts compartmentalize cellular processes contributing to the accurate spatial and temporal organization of molecules required at dendritic spines (Allen et al., 2007). Neurotrophin and neurotransmitter receptors (NTRcs) are recruited from extrasynaptic to synaptic sites through association to lipid rafts, which reduce receptor lateral mobility at the synaptic space (Nagappan and Lu, 2005; Fernandes et al., 2010). In fact, the post synapse has been proposed as a lipid raft-enriched territory and certain key structural proteins such as the postsynaptic density protein 95 (PSD95) as well as AMPARc dynamically associate to these domains (Perez and Bredt, 1998; Suzuki, 2002; Hering et al., 2003; Suzuki et al., 2011). The tight control of the turnover of phosphoinositides and their derivatives plays also a central role in spine plasticity. We next describe data available on the presence of the aforementioned lipids in spines and on their contribution to spine physiology. Hopefully, the already mentioned imaging techniques based on advanced lipid probes and super-resolution microscopy together with most sensitive quantitative measurements (i.e., liquid chromatography coupled with tandem mass spectrometry) would contribute to more precisely define the lipid composition of spines and its changes in real time in living cells.

Cholesterol

Pharmacological extraction of cholesterol or inhibition of its synthesis led to the disappearance of dendritic spines in cultured hippocampal neurons, probably mediated by disruption of the actin cytoskeleton (Hering et al., 2003). This finding defined cholesterol as a core component of spines.

Much more at link.

Protection after stroke: cellular effectors of neurovascular unit integrity

Now if we just had a great stroke association that would take this information and create translational stroke protocols to stop parts of the neuronal cascade of death. But we have crap for stroke associations and thus future survivors will continue to not have any useful stroke protocols in the first week.
http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00231/full?

Rafael Andres Posada-Duque¹, George E. Barreto² and Gloria Patricia Cardona-Gomez^1*

• ¹Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, Faculty of Medicine, Sede de Investigación Universitaria (SIU), University of Antioquia UdeA, Medellín, Colombia
• ²Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia

Neurological disorders are prevalent worldwide. Cerebrovascular diseases (CVDs), which account for 55% of all neurological diseases, are the leading cause of permanent disability, cognitive and motor disorders and dementia. Stroke affects the function and structure of blood-brain barrier, the loss of cerebral blood flow regulation, oxidative stress, inflammation and the loss of neural connections. Currently, no gold standard treatments are available outside the acute therapeutic window to improve outcome in stroke patients. Some promising candidate targets have been identified for the improvement of long-term recovery after stroke, such as Rho GTPases, cell adhesion proteins, kinases, and phosphatases. Previous studies by our lab indicated that Rho GTPases (Rac and RhoA) are involved in both tissue damage and survival, as these proteins are essential for the morphology and movement of neurons, astrocytes and endothelial cells, thus playing a critical role in the balance between cell survival and death. Treatment with a pharmacological inhibitor of RhoA/ROCK blocks the activation of the neurodegeneration cascade. In addition, Rac and synaptic adhesion proteins (p120 catenin and N-catenin) play critical roles in protection against cerebral infarction and in recovery by supporting the neurovascular unit and cytoskeletal remodeling activity to maintain the integrity of the brain parenchyma. Interestingly, neuroprotective agents, such as atorvastatin, and CDK5 silencing after cerebral ischemia and in a glutamate-induced excitotoxicity model may act on the same cellular effectors to recover neurovascular unit integrity. Therefore, future efforts must focus on individually targeting the structural and functional roles of each effector of neurovascular unit and the interactions in neural and non-neural cells in the post-ischemic brain and address how to promote the recovery or prevent the loss of homeostasis in the short, medium and long term.

Introduction

Neurological disorders are highly prevalent around the globe. In 2008, neurodegenerative disorders were responsible for 1% of disabilities worldwide (W.H.O., 2003). Strokes account for 55% of all neurological diseases and are considered the leading cause of permanent physical and mental disability (OMS, 2013). The primary risk factors of stroke include hyperlipidemia, hypertension, diabetes mellitus, and harmful habits, such as smoking and excessive alcohol consumption. The high incidence of strokes is related to an increased number of dementia cases and other emotional and cognitive disorders, such as depression and memory loss (Ovbiagele and Nguyen-Huynh, 2011). Death, physical deterioration, and altered quality of life are consequences of the natural history of strokes among patients who survive an ischemic event (Sacco, 1997, 1998; Feigin et al., 2003; Silva et al., 2006). Interestingly, the coexistence of cerebral ischemia and neurodegenerative pathologies profoundly impacts the development of dementia, suggesting a reciprocal interaction between ischemia and neurodegeneration (Nagy et al., 1997; Snowdon et al., 1997). These observations, along with the results of epidemiological studies that have indicated that Alzheimer’s disease (AD) and cerebrovascular diseases share similar risk factors (Breteler, 2000), have shifted interest to vascular factors as fundamental contributors to the pathogenesis of neurodegenerative diseases (de la Torre and Mussivand, 1993; Kalaria, 2000; Iadecola and Gorelick, 2003). This hypothesis has been supported by the experimental findings that showed that amyloid-beta (Aβ) peptide, which is commonly detected in AD patients, exhibits strong cerebrovascular effects and that ischemia-induced responses to hypoxia are potent modulators of cerebral amyloidogenesis (Iadecola, 2004). Both Aβ peptide and vascular risk factors deteriorate the structure and function of the neurovascular unit (NVU, consisting of the endothelium, glia, neurons, pericytes, and the basal lamina) (Mirra and Gearing, 1997; Snowdon et al., 1997; Breteler, 2000; Kalaria, 2000; Iadecola and Gorelick, 2003; Iadecola, 2004).

The NVU acts as a guardian of cerebral homeostasis. Neurons, glia, the perivascular space, and the endothelium are closely interrelated to maintain the homeostasis of the brain microenvironment (Iadecola, 2010), regulate blood flow, modulate the exchange across the blood-brain barrier (BBB), contribute to immune vigilance and provide trophic support to the brain (Iadecola, 2010). Substantial evidence has shown that cerebrovascular dysfunction is implicated in not only cognitive impairment (such as that of cognitive origin) but also neurodegenerative diseases, such as AD (Chui et al., 1992; Alavi et al., 1998; Kalaria, 2000; Iadecola, 2004; Simpkins et al., 2005; Hachinski et al., 2006; Pendlebury et al., 2012). Ischemic stroke is exacerbated by several risk factors that affect the function and structure of blood vessels in the brain and cells associated with the NVU, reducing the ability of the brain parenchyma to repair due to the rupture of the BBB, the loss of brain blood flow regulation, oxidative stress, inflammation, and the loss of neuronal connections, ultimately increasing brain dysfunction (Deane et al., 2003; Ohab et al., 2006; Konsman et al., 2007; Weber et al., 2007; Bell et al., 2009; Wolburg et al., 2009). The study of stroke has focused on understanding the molecular and pathophysiological mechanisms of neuronal death, recovery and pharmacological intervention strategies, as well as clinical and epidemiological characteristics (Silva et al., 2006). In addition, several molecular targets associated with endothelial dysfunction and cardio-cerebrovascular risk, including CDK5, Rho GTPases, and cell adhesion proteins, are described below and presented in a hypothetical schematic in Figure 1 to explain and propose a potential neuroprotective approach for stroke.

Much more at link.

Obesity is a risk factor for significant carotid atherosclerosis in patients aged 39 to 55 years

At age 50 when I had my stroke my right carotid artery dissected due to trauma and probably 80% atherosclerosis blockage. I was in fantastic shape, my cardiovascular fitness level was as an athlete. But since I'm an outlier no one will analyze why my plaque was so bad and maybe save others from a stroke. It is much easier to just put out fucking lazy press releases and relegate the problem solving to someone else.

Obesity is a risk factor for significant carotid atherosclerosis in patients aged 39 to 55 years

da Silva ES, et al. – Authors compared the prevalence of risk factors between young and old individuals with significant carotid atherosclerosis. Obesity and smoking were significant risk factors for young patients in this sample.

• They retrospectively reviewed the records of patients aged 39 to 55 years (group I) and aged >=60 years (group II) with significant atherosclerotic stenosis at the carotid bifurcation.
• Group I patients had significantly higher values for the following factors: weight, height, body mass index, diastolic pressure, prevalence of current smoking, total and low–density lipoprotein cholesterol and significant lower values for systolic pressure, creatinine, and prevalence of coronary artery disease.
• Group I patients were more symptomatic and showed higher rates of carotid occlusion and near occlusion.
• Atherosclerosis of the carotid bifurcation was more aggressive in the younger group, with a higher rate of occlusion and near occlusion.

Mayo Clinic - Cholesterol: Top 5 foods to lower your numbers

If you think the Mayo Clinic knows what they are talking about with cholesterol. Read it all here:
http://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/cholesterol/art-20045192/?
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1. Oatmeal, oat bran and high-fiber foods

2. Fish and omega-3 fatty acids

• Mackerel
• Lake trout
• Herring
• Sardines
• Albacore tuna
• Salmon
• Halibut

3. Walnuts, almonds and other nuts

4. Olive oil

5. Foods with added plant sterols or stanols

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And from Harvard Medical School;

CHAPTER 1: Understanding Cholesterol: The Good, the Bad, and the Necessary

Cholesterol performs three main functions:

1. It helps make the outer coating of cells.
2. It makes up the bile acids that work to digest food in the intestine.
3. It allows the body to make Vitamin D and hormones, like estrogen in women and testosterone in men.

Without cholesterol, none of these functions would take place, and without these functions, human beings wouldn't exist.

For more information or to purchase this book, follow this link:
http://www.health.harvard.edu/books/Lowering_Your_Cholesterol.htm
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And from   David Perlmutter MD Empowering neurologist

Your Brain Needs Cholesterol

Cholesterol is vitally important for brain function. While your brain represents about 2-3% of your total body weight, 25% of the cholesterol in your body is found in your brain, where it plays important roles in such things as membrane function, acts as an antioxidant, and serves as the raw material from which we are able to make things like progesterone, estrogen, cortisol, testosterone and even vitamin D.
In fact, in a recent study available on the NIH Public Access site, researchers showed that in the elderly, the best memory function was observed in those with the highest levels of cholesterol. Low cholesterol is associated with an increased risk for depression and even death.

 

 

 

Triglycerides and cardiovascular disease

I suppose I shouldn't comment on doctors  area of expertise, but I still think that they need to solve why inflammation occurs rather than the particles floating in the bloodstream. Have they never heard of cause and effect or root cause analysis. They wouldn't last a week in a programming environment. They would be fired within days for suggesting working on peripheral issues rather than solving the real problem.  But then this is somebody else's problem, no need to really worry about it. I'll get paid regardless.  Pay for performance would solve that problem or having business rules apply to doctors.
http://www.mdlinx.com/internal-medicine/newsl-article.cfm/5485946/ZZF307965849E94474BB34FC062CEC0F93/?
Nordestgaard BG, et al. – After the introduction of statins, clinical emphasis first focussed on LDL cholesterol–lowering, then on the potential for raising HDL cholesterol, with less focus on lowering triglycerides.

• However, the understanding from genetic studies and negative results from randomised trials that low HDL cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides.
• This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride–rich lipoproteins as an additional cause of cardiovascular disease and all–cause mortality.
• Triglycerides can be measured in the non–fasting or fasting states, with concentrations of 2—10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk of acute pancreatitis and possibly cardiovascular disease.
• Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride–lowering drugs are being developed, and large–scale trials have been initiated that will hopefully provide conclusive evidence as to whether lowering triglycerides reduces the risk of cardiovascular disease.