Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders

You just might want your doctor and hospital to contact researchers to follow this up with human testing for the improvement of cognitive decline possibility. Up to you, YOUR HOSPITAL WILL DO NOTHING WITHOUT YOUR PRODDING. 

Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders

Dwivedi D¹,

Megha K¹,

Mishra R¹,

Mandal PK¹

Author information

Neurochemical Research, 14 Apr 2020,
DOI: 10.1007/s11064-020-03030-1 PMID: 32297027 

Review

Abstract 

---

Glutathione (GSH) is an important antioxidant found abundantly and synthesized intracellularly in the cytosol in a tightly regulated fashion. It has diverse physiological functions, including protection against reactive oxygen species and nitrogen species, antioxidant defense as well as maintenance of cellular thiol status. The human brain due to the high oxygen consumption is extremely susceptible to the generation of reactive oxygen species. GSH plays a paramount role in brain antioxidant defense, maintaining redox homeostasis. The depletion of brain GSH has also been observed from both autopsies as well as in vivo MRS studies with aging and varied neurological disorders (Alzheimer's disease, Parkinson's disease, etc.). Therefore, GSH enrichment using supplementation is a promising avenue in the therapeutic development for these neurological disorders. This review will enrich the information on the importance of GSH synthesis, metabolism, functions, compartmentation and inter-organ transport, structural conformations and its quantitation via different techniques. The transportation of GSH in the brain via different interventional routes and its potential role in the development of therapeutic strategies for various brain disorders is also addressed. Very recent study found significant improvement of behavioral deficits including cognitive decline, depressive-like behaviors, in APP (NL-G-F/NL-G-FG-) mice due to oral GSH administration. This animal model study put an emergent need to complete GSH supplementation trial in MCI and AD patients for cognitive improvement as proposed earlier.

Intermittent fasting increases adult hippocampal neurogenesis

Now you need your doctors and hospital to initiate human research in this and specify how these newly created neurons will migrate to needed areas.  

Maybe these might help:

• Interkinetic nuclear migration (1)
• migration (41)
• transendothelial migration (1)

Intermittent fasting increases adult hippocampal neurogenesis

Sang‐Ha Baik, ¹ Vismitha Rajeev, ¹ David Yang‐Wei Fann, ¹ Dong‐Gyu Jo, ² and Thiruma V. Arumugam ^{1 , 2 , 3}

Author information Article notes Copyright and License information Disclaimer

Associated Data

Data Availability Statement

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Abstract

Introduction

Intermittent fasting (IF) has been suggested to have neuroprotective effects through the activation of multiple signaling pathways. Rodents fasted intermittently exhibit enhanced hippocampal neurogenesis and long‐term potentiation (LTP) at hippocampal synapses compared with sedentary animals fed an ad libitum (AL) diet. However, the underlying mechanisms have not been studied. In this study, we evaluated the mechanistic gap in understanding IF‐induced neurogenesis.

Methods

We evaluated the impact of 3 months of IF (12, 16, and 24 hr of food deprivation on a daily basis) on hippocampal neurogenesis in C57BL/6NTac mice using immunoblot analysis.

Results

Three‐month IF significantly increased activation of the Notch signaling pathway (Notch 1, NICD1, and HES5), neurotrophic factor BDNF, and downstream cellular transcription factor, cAMP response element‐binding protein (p‐CREB). The expression of postsynaptic marker, PSD95, and neuronal stem cell marker, Nestin, was also increased in the hippocampus in response to 3‐month IF.

Conclusions

These findings suggest that IF may increase hippocampal neurogenesis involving the Notch 1 pathway.

Keywords: brain‐derived neurotrophic factor, hippocampus, intermittent fasting, neurogenesis, Notch

Go to:

Abstract

Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. The present study has sought to investigate the relationship between IF and hippocampal neurogenesis. Our findings suggest that IF may increase hippocampal neurogenesis involving the Notch 1 pathway.

Go to:

1. INTRODUCTION

Dietary restriction (DR) is defined as a decrease in energy consumption without reducing nutritional value. This simple dietary intervention has been shown in a wide range of experimental animals to extend lifespan and decrease the incidence of several age‐related diseases. The definition of DR has been expanded from an alternative description of caloric restriction (CR) to also encompass a broader scope of interventions, including short‐term starvation, periodic fasting, fasting‐mimetic diets, and intermittent fasting (IF; Mattson & Arumugam, 2018). IF has been proven to be advantageous to various organ systems in the body and acts as a mild metabolic stressor. It has been postulated that IF is able to cause powerful changes in the metabolic pathways in the brain via an increase in stress resistance, and breakdown of ketogenic amino acids and fatty acids (Bruce‐Keller, Umberger, McFall, & Mattson, 1999; Kim et al., 2018). Experimental studies have also shown that IF is neuroprotective against acute brain injuries such as stroke, and neurodegenerative diseases (Arumugam et al., 2010; Halagappa et al., 2007; Manzanero et al., 2014). In addition, recent studies have also shown that IF can lead to an increase in neurogenesis levels in the hippocampus (Manzanero et al., 2014).

In the adult brain, the niches of neuronal stem cells (NSCs) are located specifically at the subventricular zone (SVZ) of the lateral ventricles, and in the subgranular zone (SGZ) of the hippocampus. The ability of NSCs to maintain cerebral neurogenesis is controlled by the tight regulation of balanced events commencing from stem cell maintenance, to stem cell division and proliferation, to its differentiation into mature neurons, and finally their survival and functional integration into the brain parenchyma (Lathia, Mattson, & Cheng, 2008; Lledo, Alonso, & Grubb, 2006). The process of adult neurogenesis is highly regulated and is adaptable to environmental, morphological, and physiological cues, whereby cerebral performance is suited to function at optimal levels for a given environment. Studies have demonstrated that the proliferation of neural stem cells can be modified through metabolic perturbations experienced during high temperatures (Matsuzaki et al., 2009), physical activity (Niwa et al., 2016), and a high‐fat diet (Kokoeva, Yin, & Flier, 2005). Experimental studies from our group have also shown that IF increases neurogenesis in the hippocampus as a form of neuroprotection following acute brain injury such as ischemic stroke. Moreover, we established that the number of BrdU‐labeled cells in the dentate gyrus of IF mice was elevated (Manzanero et al., 2014). To measure cell proliferation without the confound availability of an exogenous marker BrdU, we established increases in the number of Ki67‐labeled cells in the dentate gyrus of mice on the IF diet, indicating enhancement of cell proliferation in these mice (Manzanero et al., 2014). In addition to our findings, previous work similarly demonstrated that using the every other day (EOD) IF regimen also increased BrdU‐labeled cell number in the hippocampus (Lee, Duan, & Mattson, 2002).

However, the molecular process involved in IF‐induced neurogenesis is not well understood. The Notch signaling pathway that is intricately involved in the determination of cell fate during brain development and adult neurogenesis may be a possible molecular process involved in IF‐induced neurogenesis (Lathia et al., 2008). In this study, we investigated the expression levels of molecular and cellular components of the hippocampal region, focusing specifically on Notch activation and associated proteins that are known to promote hippocampal neurogenesis such as brain‐derived neurotrophic factor (BDNF) and cAMP response element‐binding protein (CREB).

More at link.

Facilitation of Auditory Comprehension After Theta Burst Stimulation of Wernicke's Area in Stroke Patients: A Pilot Study

Since the effect is transitory you will need to have your doctor and stroke hospital followup with researchers to ensure research on how to make this permanent is done.

Facilitation of Auditory Comprehension After Theta Burst Stimulation of Wernicke's Area in Stroke Patients: A Pilot Study

Viviana Versace^1,2*, Kerstin Schwenker^3,4, Patrick B. Langthaler³, Stefan Golaszewski^3,4, Luca Sebastianelli^1,2, Francesco Brigo^5,6, Elke Pucks-Faes⁷, Leopold Saltuari^2,7 and Raffaele Nardone^3,4,5

• ¹Department of Neurorehabilitation, Hopsital of Vipiteno-Sterzing, Vipiteno-Sterzing, Italy
• ²Research Unit for Neurorehabilitation of South Tyrol, Bolzano, Italy
• ³Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
• ⁴Karl Landsteiner Institut für Neurorehabilitation und Raumfahrtneurologie, Salzburg, Austria
• ⁵Department of Neurology, Franz Tappeiner Hospital, Merano, Italy
• ⁶Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy
• ⁷Department of Neurology, Hochzirl Hospital, Zirl, Austria

Introduction: 

Single-pulse transcranial magnetic stimulation (TMS) and high-frequency repetitive TMS (rTMS) over Wernicke's area were found to facilitate language functions in right-handed healthy subjects. We aimed at investigating the effects of excitatory rTMS, given as intermittent theta burst stimulation (iTBS) over left Wernicke's area, on auditory comprehension in patients suffering from fluent aphasia after stroke of the left temporal lobe.

Methods: 

We studied 13 patients with chronic fluent aphasia after an ischemic stroke involving Wernicke's area. iTBS was applied in random order to Wernicke's area, the right-hemisphere homologous of Wernicke's area, and the primary visual cortex. Auditory comprehension was blind assessed using the Token test before (T0), 5 (T1), and 40 min (T2) after a single session of iTBS.

Results: 

At the first evaluation (T1) after iTBS on left Wernike's area, but not on the contralateral homologous area nor on the primary visual cortex, the scores on the Token test were significantly increased. No significant effects were observed at T2.

Conclusion: 

We demonstrated that a single session of excitatory iTBS over Wernicke's area was safe and led to a transient facilitation of auditory comprehension in chronic stroke patients with lesions in the same area. Further studies are needed to establish whether TBS-induced modulation can be enhanced and transformed into longer-lasting effects by means of repeated TBS sessions and by combining TBS with speech and language therapy.

Blood test may predict cardiovascular disease

You can tell the competency of your doctor and hospital if they do nothing to ensure further research is done. Hope you are ok with such incompetency. I bet they did nothing with these earlier posts and of course our fucking failures of stroke associations did nothing either.

• elevated troponin (2 posts from Nov. 2018)
• troponin T (1 post from June 2013) 

 

 

Blood test may predict cardiovascular disease

Healthline/Medical News Today | May 01, 2019

Advertisement

New research suggests that a simple blood test, which doctors currently use to diagnose heart attacks, may be useful in predicting the risk of cardiovascular disease.
According to the latest statistics from the American Heart Association (AHA), almost half of the people living in the United States have some form of cardiovascular disease. In fact, according to 2016 figures, 121.5 million US adults, or 48% of the entire population, have cardiovascular disease (CVD), which is a cluster of conditions that includes hypertension. Doctors often call hypertension the "silent killer" because it does not show any visible symptoms until it is too late.
The same AHA report predicts that by 2035, over 130 million adults will have a form of CVD that could bring costs in the United States to 1.1 trillion dollars. Currently, heart disease is the leading cause of death in the United States, while stroke is the fifth.
But what if there was a blood test that could accurately predict whether a person will have heart disease or a stroke? New research suggests that such a test may already exist. By detecting the blood levels of specific proteins that heart muscles release when they are injured, scientists may be able to predict a person's risk of eventually developing CVD.
Dr. Christie Ballantyne, who is the cardiology chief at Baylor College of Medicine in Houston, TX, and his team, detail this idea in a new study that appears in the AHA journal Circulation.

Troponin levels can predict CVD risk

Troponins are proteins that signal heart muscle damage, and in the new research, Dr. Ballantyne and his colleagues wanted to see if detecting troponin in the blood of healthy middle-aged adults or seniors could predict CVD risk.
Dr. Ballantyne and colleagues analyzed a group of 8,121 people aged 54–74 who participated in the "Atherosclerosis Risk in Communities" study. None of the participants had a history of cardiovascular disease. The scientists identified troponin levels in 85% of the participants and applied Cox proportional hazards models to examine the links between these levels and cardiovascular disease. Namely, they studied correlations with coronary heart disease, myocardial infarction, ischemic stroke, atherosclerotic cardiovascular disease, heart failure hospitalization, global cardiovascular disease, and all-cause mortality.

• See Also: Study questions long-term heart benefits of tight blood sugar control

The research found that high levels of troponin correlated strongly with "increased global CVD incidence in the general population independent of traditional risk factors." High-sensitivity troponin tests, therefore, proved to be an accurate way of predicting CVD risk, especially when combined with a standard method of calculating a person's 10-year cardiovascular risk.
"What we're finding out is that these tests can be used in the general population to give us information as to who is most likely to have a future problem, whether it be a heart attack, stroke, or heart failure," says Dr. Ballantyne. "If you can treat someone much earlier, before [they] have symptoms, you will be far more effective in preventing events," continues the researcher, who adds, "Our major problem is that we do too little, too late."

"If the first time you find out that you're at risk for heart failure is when you actually start getting short of breath and you end up in the hospital, you probably have advanced heart disease already, and it is going to be harder to treat than if that person took steps years earlier."
—Dr. Ballantyne

Instead, knowing the risk in advance can prompt people to take preventive measures, such as exercising more and watching their blood pressure. However, the scientists explain that although doctors currently use troponin tests to diagnose a heart attack, they do not yet accept them as a tool for predicting risk. Scientists need to do more research before using these tests to evaluate risk.
"Research in this area is leading us toward individualized care more and more, so we can better predict who's at risk for developing adverse cardiovascular outcomes," comments Dr. Rebecca Vigen, an assistant professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, who did not participate in the research. "This study is a step in the direction of personalizing care," Dr. Vigen says.

• See Also: Intensive glucose control in patients with type 2 diabetes — 15-year follow-up

Read the full article on Healthline/Medical News Today

Large-scale changes in cortical dynamics triggered by repetitive somatosensory electrical stimulation

What is your stroke hospital doing to ensure human testing will occur on this? Or are they once again being fucking incompetent? Comeuppance will eventually hit a lot of these people and they will finally realize how stupid they were.

Large-scale changes in cortical dynamics triggered by repetitive somatosensory electrical stimulation

• April K. Hishinuma,
• Tanuj Gulati,
• Mark J. Burish and
• Karunesh GangulyEmail authorView ORCID ID profile

Journal of NeuroEngineering and Rehabilitation201916:59

https://doi.org/10.1186/s12984-019-0520-1

©  The Author(s). 2019

• Received: 30 October 2018
• Accepted: 29 March 2019
• Published: 24 May 2019

Abstract

Background

Repetitive somatosensory electrical stimulation (SES) of forelimb peripheral nerves is a promising therapy; studies have shown that SES can improve motor function in stroke subjects with chronic deficits. However, little is known about how SES can directly modulate neural dynamics. Past studies using SES have primarily used noninvasive methods in human subjects. Here we used electrophysiological recordings from the rodent primary motor cortex (M1) to assess how SES affects neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics.

Methods

We performed acute extracellular recordings in 7 intact adult Long Evans rats under ketamine-xylazine anesthesia while they received transcutaneous SES. We recorded single unit spiking and local field potentials (LFP) in the M1 contralateral to the stimulated arm. We then compared neural firing rate, spike-field coherence (SFC), and power spectral density (PSD) before and after stimulation.

Results

Following SES, the firing rate of a majority of neurons changed significantly from their respective baseline values. There was, however, a diversity of responses; some neurons increased while others decreased their firing rates. Interestingly, SFC, a measure of how a neuron’s firing is coupled to mesoscale oscillatory dynamics, increased specifically in the δ-band, also known as the low frequency band (0.3- 4 Hz). This increase appeared to be driven by a change in the phase-locking of broad-spiking, putative pyramidal neurons. These changes in the low frequency range occurred without a significant change in the overall PSD.

Conclusions

Repetitive SES significantly and persistently altered the local cortical dynamics of M1 neurons, changing both firing rates as well as the SFC magnitude in the δ-band. Thus, SES altered the neural firing and coupling to ongoing mesoscale dynamics. Our study provides evidence that SES can directly modulate cortical dynamics.

Keywords

• Somatosensory electrical stimulation (SES)
• Peripheral nerve
• Spiking dynamics
• Motor cortex
• Low frequency oscillations

Background

Somatosensory input is essential for skilled movements [1, 2, 3]; this is particularly true for dexterous movements [1, 4, 5, 6]. Interestingly, the somatosensory system has been shown to experience relatively rapid bidirectional changes in organization as a result of repetitive manipulations of peripheral inputs. Consistent with this notion are seminal studies in both animals and humans which demonstrated that reductions in sensory feedback, either by denervation or ischemic nerve block, induced changes in motor representations [7, 8].

Studies have also shown that increases in afferent input by stimulating peripheral pathways (i.e. repetitive somatosensory electrical stimulation or SES) can alter sensorimotor representations of the stimulated body part [9, 10]. One of the first studies examining this neuromodulation method found that sensory stimulation of oral structures resulted in prolonged changes in excitability as well as an increase in the area of representation determined using functional imaging [11]. Consistent with these results are studies demonstrating that altered patterns of physical contacts to the fingers can also persistently reorganize sensory maps [12, 13]. Importantly, repetitive SES has also proven to be a promising therapeutic tool for motor rehabilitation [10, 14, 15, 16].

In both humans and rodents, SES can increase excitability as measured by responses to transcranial magnetic stimulation (TMS) pulses [9, 17]. Past studies have used non-invasive measures to examine cortical excitability such as motor evoked potentials (MEPs) with TMS [9, 17] and cortical reorganization using blood oxygenation signals [11]. It remains unclear what are the precise mechanisms underlying these changes. For example, the observed change in the evoked MEPs following SES may occur without changes in brainstem electrical stimulation-evoked potentials or spinal reflexes [9, 18, 19]. This suggests the possibility that the cortex may be an important site of plasticity. While our recent study showed that SES can also modify low-frequency dynamics as measured using electroencephalogram (EEG) [20], it remains unclear if these changes are local to cortex. Invasive electrophysiology offers one method to assess if SES can directly alter local motor cortical dynamics.

While the body of literature summarized above has provided important mechanistic insight, little is known about how SES interacts with ongoing cortical dynamics at the level of single neurons and groups of neurons, or neural ensembles. Single neurons are a fundamental unit of the nervous system. The coordinated firing of neural ensembles, e.g. co-firing of neurons in a temporally coupled manner, is now also recognized as an important module for information processing [21, 22, 23, 24, 25, 26]. In addition, oscillations may provide a mechanism for dynamic coordination of ensembles across motor and sensory areas [21, 22, 23, 24, 25, 27]. Oscillations likely reflect synchronized rhythmic excitability linked to coordinated firing of neurons [28]. Our collective understanding of both single neuron and ensemble firing patterns has greatly improved our understanding of how neural activity patterns underlie complex sensory and motor behaviors. Similarly, it is likely that such activity may play an important role in driving neural plasticity after injury and during neuromodulation using methods such as SES.

The goal of this study was to develop a model of the cortical effects of SES using high-resolution, invasive recording of neurons. We were particularly interested in understanding the diversity of single neuron responses to SES. It is unlikely that all neurons respond identically to a given perturbation. This may be, in part, the result of the multiple cell-types in a given region and the diversity of network connectivity for single neurons [29]. We also wanted to compare changes in neural activity related to larger scale network oscillatory activity. More specifically, we examined the effects of SES on primary motor cortex (M1) at the level of single neuron firing rates as well as the neural coupling to ongoing spontaneous oscillations. We found that SES could independently change both the firing rate and the phase locking, i.e. the consistency of the neural firing relative to oscillatory dynamics. Together, our results provide evidence that SES can directly modulate neural dynamics in M1.

With grit and gratitude, stroke survivor plays on

Recovery should not require grit. Your doctor should have all the skills and stroke protocols that get you 100% recovered. Starting with stoppingthe 5 causes of the neuronal cascade of death in the first week. This is what is wrong with stroke, the doctor has NO responsibility for getting you recovered, everything is put on your shoulders with NO PROTOCOLS to guide you.  If your doctor assumed responsibility every survivor that didn't get recovered would have an analysis as to why and a plan developed to solve that for next time. But that isn't what occurs. My opinion is that this is massive incompetence on the part of any part of the stroke medical world that doesn't do followup and initiate research to solve stroke. The status quo is a complete failure.

Not getting you 100% recovered is failure on your doctor and stroke hospitals part.

 

With grit and gratitude, stroke survivor plays on

By American Heart Association News

Stroke survivor Dave Kim at the Red Cross Gala in San Francisco. (Photo courtesy of Dave Kim)

Dave Kim can hardly remember a time he wasn't making music. He plays three instruments – most notably the electric violin – and has performed at countless weddings and in concerts around the world, opening for such acts as Hootie and the Blowfish.
So after having a stroke in August 2016 at age 42, he called upon his music training to help him recover.
While in intensive care, Kim used what strength he had to focus, not on the proper notes or certain chords or harmonies, but on his right thumb. He willed that thumb to move. On Day Five, it did.
Then came research, including the discovery that the way musicians' brains were formatted could help aid stroke recovery.
"When communication cuts off from the brain to the limbs," he said, "the brain finds other ways to communicate with the limbs." That ability is called neuroplasticity. Reading about it gave Kim impetus to work on each finger, each arm, each leg.
"I found that everything I've done in my life is therapy," he said.

Dave Kim recuperates in the hospital after his stroke. (Photo courtesy of Dave Kim)

Kim had his stroke while recording a music video in his California home. While playing, his right arm gave way. Then his right leg went limp. He was able to call a doctor friend. A neighbor drove him to the hospital. Kim's blood pressure was measured at a dangerous 230/130. An MRI showed a blood clot in the brain.
The stroke left him unable to stand, much less play his beloved instruments. He felt trapped in his body and, he said, "buried alive." He feared being in the hospital forever and nobody remembering him.
But when Kim shared his plight on social media, dozens and dozens of fans and friends came to visit. They posted well wishes. Their support overwhelmed his spirits.
"I do matter," Kim realized.
Longtime friend Will O'Brien said that when he visited Kim in the hospital, he could sense a change. Not in the obvious physical way, but more deeply. The stroke, he said, gave Kim "a new lease on life. It was one of those tragic events he turned into a true blessing."
After leaving the hospital, Kim spent three weeks in rehab, working to regain the ability to walk, to play music, to do everyday tasks often taken for granted. He also learned about strokes – which he, like many people, thought only happen to the elderly.
Looking back, he sees signs that pointed the way to his stroke. Each of his parents had had one. He was overweight and not eating a healthy diet. He didn't exercise. His cholesterol level and his blood pressure were high. And while he cherished time with his two young sons, raising them as a single parent was stressful.

Dave Kim, with his sons Brandon (left) and Christian, before his stroke. (Photo courtesy of Dave Kim)

Kim is now on medications that have helped lower his blood pressure and reduce his cholesterol. He's eating better. He's lost weight and has a lot more energy. And he's changed for the better in another way, too, because of something he gleaned while at the hospital: Acceptance.
"Once I had acceptance, I kind of had some gratitude," he said. "I've had a tremendous life."
When something tragic happens to people, O'Brien said, it brings out their true character. They ask, "Who am I at the core?" And, "Is this a chance to be a victim or to bring a message of positivity?"
Kim chose positivity.
He now uses his experience and his talent to help others in such ways as speaking out on stroke awareness. And though he made his name by recording popular music, his life mission now is to inspire people through mindful and meditative music.
"For sure I've learned about myself," he said. "I just have a lot of grit, a lot of gratitude, and confidence to believe in myself."
Stories From the Heart chronicles the inspiring journeys of heart disease and stroke survivors, caregivers and advocates.
If you have questions or comments about this story, please email editor@heart.org.

Neural stem cells harvested from live brains by antibody-conjugated magnetic nanoparticles

Well, now for some followup from your doctor, your stroke hospital, your

fucking failures of stroke associations.  I have billions of neurons needed. But nothing will occur since we have NO STROKE LEADERSHIP to ask them to followup and execute the stroke strategy.  This might be the only way I ever fully recover.

Neural stem cells harvested from live brains by antibody-conjugated magnetic nanoparticles

Lui CN¹, Tsui YP, Ho AS, Shum DK, Chan YS, Wu CT, Li HW, Tsang SC, Yung KK.

Author information

Abstract

It stems from the magnetism: The extraction of stem/progenitor cells from the brain of live animals is possible using antibodies conjugated to magnetic nanoparticles (Ab-MNPs). The Ab-MNPs are introduced to a rat's brain with a superfine micro-syringe. The stem cells attach to the Ab-MNPs and are magnetically isolated and removed. They can develop into neurospheres and differentiate into different types of cells outside the subject body. The rat remains alive and healthy.

Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

antibodies; magnetic nanoparticles; nanoparticles; regenerative medicine; stem cells

PMID:

24108547

DOI:

10.1002/anie.201305482

[Indexed for MEDLINE]

Blood test may predict cardiovascular disease

You can tell the competency of your doctor and hospital if they do nothing to ensure further research is done. Hope you are ok with such incompetency. I bet they did nothing with these earlier posts and of course our fucking failures of stroke associations did nothing either.

• elevated troponin (1post from Nov. 2018)
• troponin T (1 post from June 2013) 

 

Blood test may predict cardiovascular disease

Healthline/Medical News Today | May 01, 2019

New research suggests that a simple blood test, which doctors currently use to diagnose heart attacks, may be useful in predicting the risk of cardiovascular disease.

Advertisement

According to the latest statistics from the American Heart Association (AHA), almost half of the people living in the United States have some form of cardiovascular disease. In fact, according to 2016 figures, 121.5 million
US adults, or 48% of the entire population, have cardiovascular disease (CVD), which is a cluster of conditions that includes hypertension. Doctors often call hypertension the "silent killer" because it does not show any visible symptoms until it is too late. The same AHA report predicts that by 2035, over 130 million adults will have a form of CVD that could bring costs in the United States to 1.1 trillion dollars. Currently, heart disease is the leading cause of death in the United States, while stroke is the fifth.
But what if there was a blood test that could accurately predict whether a person will have heart disease or a stroke? New research suggests that such a test may already exist. By detecting the blood levels of specific proteins that heart muscles release when they are injured, scientists may be able to predict a person's risk of eventually developing CVD.

• See Also: Association between high blood PCB levels and premature death

Dr. Christie Ballantyne, who is the cardiology chief at Baylor College of Medicine in Houston, TX, and his team, detail this idea in a new study that appears in the AHA journal Circulation.

Troponin levels can predict CVD risk

Troponins are proteins that signal heart muscle damage, and in the new research, Dr. Ballantyne and his colleagues wanted to see if detecting troponin in the blood of healthy middle-aged adults or seniors could predict CVD risk.
Dr. Ballantyne and colleagues analyzed a group of 8,121 people aged 54–74 who participated in the "Atherosclerosis Risk in Communities" study. None of the participants had a history of cardiovascular disease. The scientists identified troponin levels in 85% of the participants and applied Cox proportional hazards models to examine the links between these levels and cardiovascular disease. Namely, they studied correlations with coronary heart disease, myocardial infarction, ischemic stroke, atherosclerotic cardiovascular disease, heart failure hospitalization, global cardiovascular disease, and all-cause mortality.
The research found that high levels of troponin correlated strongly with "increased global CVD incidence in the general population independent of traditional risk factors." High-sensitivity troponin tests, therefore, proved to be an accurate way of predicting CVD risk, especially when combined with a standard method of calculating a person's 10-year cardiovascular risk.
"What we're finding out is that these tests can be used in the general population to give us information as to who is most likely to have a future problem, whether it be a heart attack, stroke, or heart failure," says Dr. Ballantyne. "If you can treat someone much earlier, before [they] have symptoms, you will be far more effective in preventing events," continues the researcher, who adds, "Our major problem is that we do too little, too late."

"If the first time you find out that you're at risk for heart failure is when you actually start getting short of breath and you end up in the hospital, you probably have advanced heart disease already, and it is going to be harder to treat than if that person took steps years earlier."
—Dr. Ballantyne

Instead, knowing the risk in advance can prompt people to take preventive measures, such as exercising more and watching their blood pressure. However, the scientists explain that although doctors currently use troponin tests to diagnose a heart attack, they do not yet accept them as a tool for predicting risk. Scientists need to do more research before using these tests to evaluate risk.
"Research in this area is leading us toward individualized care more and more, so we can better predict who's at risk for developing adverse cardiovascular outcomes," comments Dr. Rebecca Vigen, an assistant professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, who did not participate in the research. "This study is a step in the direction of personalizing care," Dr. Vigen says.

• See Also: Common oral infections in childhood may increase the risk of atherosclerosis in adulthood

To read more, click here.

One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?

Ask your doctor and stroke hospital to followup and see how close to regular use this is. Survivors should be able to benefit. 

One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?

By Carl Zimmer

• April 2, 2019

In 2011, Dr. Dena Dubal was hired by the University of California, San Francisco, as an assistant professor of neurology. She set up a new lab with one chief goal: to understand a mysterious hormone called Klotho.

Dr. Dubal wondered if it might be the key to finding effective treatments for dementia and other disorders of the aging brain. At the time, scientists only knew enough about Klotho to be fascinated by it.

Mice bred to make extra Klotho lived 30 percent longer, for instance. But scientists also had found Klotho in the brain, and so Dr. Dubal launched experiments to see whether it had any effect on how mice learn and remember.

The results were startling. In one study, she and her colleagues found that extra Klotho protects mice with symptoms of Alzheimer’s disease from cognitive decline. “Their thinking, in every way that we could measure them, was preserved,” said Dr. Dubal.

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She and her colleagues also bred healthy mice to make extra Klotho. They did better than their fellow rodents on learning mazes and other cognitive tests.

Klotho didn’t just protect their brains, the researchers concluded — it enhanced them. Experiments on more mice turned up similar results.

“I just couldn’t believe it — was it true, or was it just a false positive?” Dr. Dubal recalled. “But here it is. It enhances of cognition even in a young mouse. It makes them smarter.”

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Five years have passed since Dr. Dubal and her colleagues began publishing these extraordinary results. Other researchers have discovered tantalizing findings of their own, suggesting that Klotho may protect against other neurological disorders, including multiple sclerosis and Parkinson’s disease.

Now Dr. Dubal and other researchers are trying to build treatments based on these results. Either by injecting Klotho into the body or by stimulating the brain to make more of the hormone, they hope to treat diseases like Alzheimer’s.

The researchers developing these treatments readily acknowledge that they may fail. And other Klotho experts think there’s a huge amount of work left to do first to figure out how Klotho affects the brain.

“You’ve got all of this amazing stuff showing a really major impact, but we can’t really explain why,” said Gwendalyn D. King, a neuroscientist at the University of Alabama at Birmingham. “That’s where we’re stuck.”

But what happens if scientists get unstuck? What if a drug that enhances cognition really were possible?

Eric Juengst, the director of the University of North Carolina Center for Bioethics, has been thinking about these questions for two decades — back when such drugs were little more than thought experiments.

We tend to think of drugs that enhance performance — say, sports doping — as bad. Drugs that cure or prevent diseases are good. “The scientific community and the public all draw that line,” said Dr. Juengst.

When it comes to Klotho, there may be no such line. In theory, such a drug might offer both a way to prevent diseases of the brain and to enhance it.

Recent research is giving these questions a sudden urgency, according to Dr. Juengst.

“It’s exciting for someone who’s been doing armchair work on this for a long time to see it happening in the real world,” he said. “But it also makes it all the more pressing that this conversation get started in earnest.”

The rest is behind the NYTimes paywall unless it is one of the free articles you can get. 

Flashing Light, Sound Restore Memory in Alzheimer's Mice

Is your stroke hospital and doctors going to do one damn thing to see this gets tested in humans? Or will they sit with their heads up their asses sucking on their thumbs waiting for SOMEONE ELSE TO SOLVE THE PROBLEM? 

 

Flashing Light, Sound Restore Memory in Alzheimer's Mice Flashing Light, Sound Restore Memory in Alzheimer's Mice

 

An innovative light and sound stimulation therapy reduced the number of amyloid plaques found in the brains of laboratory mice with Alzheimer's disease, improving memory and cognitive function. Could an hour of light and sound a day keep Alzheimer's at bay in people?
Alzheimer's disease is a type of degenerative brain disease that causes memory loss and language problems. Over 5.8 million Americans are currently living with Alzheimer's disease, including one in 10 people age 65 or older, according to the Alzheimer's Association.
The disease is caused by the buildup of two proteins in the brain—amyloid beta and tau—that clump together to form plaques or neurofibrillary tangles that impair memory function.
The research was published March 14 in Cell.
The noninvasive treatment induces brain waves called gamma oscillations.
Alzheimer's patients have impairments in gamma-frequency oscillations. Although the exact function of these oscillations, which range from 25-90 hertz, is unknown, it's believed to contribute to attention perception and memory in the brain.
In 2016, Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory, and her team exposed laboratory mice that genetically predisposed to Alzheimer's disease to a light flickering at 40 hertz for one hour a day. They found that this treatment reduced the levels of tau and amyloid beta in visual cortex of the brain and stimulated the activity of debris-clearing immune cells.
For the current study, Tsai and her team sought to improve on these results. By adding sound stimuli, they hoped the treatment would be able to reach other brain regions.
They played a 40-hertz tone one hour a day for seven hours for laboratory mice predisposed to Alzheimer's disease. At the conclusion of the study, the mice had dramatically lowered levels of beta amyloid in the auditory cortex, which process sound, and the brain's memory center, the hippocampus.
The treated mice also displayed improvements in cognition when navigating a maze that required them to remember key landmarks.
Next, the researchers administered both light and sound together. This had an even greater effect than either one given alone. Amyloid plaques reduced throughout a greater part of the brain, including teh prefrontal cortex, where higher cognitive functions take place.
Preliminary safety tests for this type of brain stimulation have already been performed in healthy human subjects, although more research is needed to determine if the treatment will work in people with Alzheimer's disease.
"As our intervention is completely non-invasive, there is minimal safety concerns. We still need to conduct human trials to determine if this is effective," Tsai said.

PTSD with other factors increase risk for CVD

Totally ignored other causes of PTSD so more research will need to be done for stroke caused PTSD.  Bad research.

With your 23% chance of stroke survivors getting PTSD

what treatments is your doctor prescribing? 

You may need this so you better hope like hell that your doctor and stroke hospital know enough to be creating this type of research.

 

 

PTSD with other factors increase risk for CVD

Scherrer J, et al. J Am Heart Assoc. 2019;doi:10.1161/JAHA.118.011133

February 13, 2019

The increased risk for CVD in patients with PTSD was associated with psychiatric and physical conditions, in addition to smoking, according to a study published in the Journal of the American Heart Association.
“This suggests there is no single comorbidity or behavior that explains the link between PTSD and cardiovascular disease,” Jeffrey Scherrer, PhD, professor and director of the division of research in the department of family and community medicine at the Saint Louis University School of Medicine, said in a press release. “Instead, a combination of physical disorders, psychiatric disorders and smoking — that are more common in patients with PTSD vs. without PTSD — appear to explain the association between PTSD and developing cardiovascular disease.”

See Also

• CVD risk fluctuates in India by region
• In diabetes with CVD, traditional risk factor modification remains top priority
• PTSD increases long-term MI, stroke risk in World Trade Center response crews

Researchers analyzed Veterans Affairs electronic medical record data from 4,178 patients (mean age, 50 years; 87% men) who had two or more visits to a VA medical center between 2008 and 2012. Patients were either in the PTSD group (n = 2,519; mean age, 49 years; 87% men) or the control group (n = 1,659; mean age, 52 years; 87% men).
Data that were assessed included vital signs, diagnosis codes, medications, laboratory results, type of clinic encounter and demographic data. Patients did not have CVD for at least 1 year before the index date, which was defined as either the second visit to a clinic for the control group or the second visit with a PTSD diagnosis for those in the PTSD group.
PTSD was significantly linked to incident CVD after adjusting for age (HR = 1.41; 95% CI, 1.21-1.63). This relationship weakened but remained significant after adjusting for physical conditions (HR = 1.23; 95% CI, 1.06-1.44).
The association between PTSD and CVD was no longer present after adjusting for sleep disorders, substance abuse/dependence, smoking and other anxiety disorder and depression diagnoses (HR = 0.96; 95% CI, 0.81-1.15).
“Recognizing that PTSD does not preordain CVD may empower patients to seek care to prevent and/or manage CVD risk factors,” Scherrer and colleagues wrote. “Patients without PTSD are also at risk of CVD if they smoke, have sleep disorder, depression or metabolic disease. In both patient populations, the risk of CVD can be mitigated with health behavior change and effective chronic disease management.” – by Darlene Dobkowski
Disclosures: The study was supported by the NHLBI. Scherrer reports he receives compensation as an editor for Family Practice. Please see the study for all other authors’ relevant financial disclosures.

Simple Drug Combination Creates New Neurons from Neighboring Cells

Now we just need followup to know how fast this drug cocktail needs to be delivered to actually work. I am assuming that my 13 years out is way too far gone.  What are your doctors and stroke hospital doing to ensure this research is translated into real world applications? You do want your children and grandchildren to have this available, don't you? Then call your stroke hospital president and demand followup on this.

Simple Drug Combination Creates New Neurons from Neighboring Cells

Neuroscience NewsFebruary 7, 2019

FeaturedNeuroscienceOpen Neuroscience Articles6 min read

Summary: Researchers have identified a small set of molecules that can convert glial cells into new neurons. The finding could help develop new treatments for Alzheimer’s disease and brain injuries.
Source: Penn State.
A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimer’s disease, and brain injuries. A team of researchers at Penn State identified a set of four, or even three, molecules that could convert glial cells–which normally provide support and insulation for neurons–into new neurons. A paper describing the approach appears online in the journal Stem Cell Reports on February 7, 2019.
“The biggest problem for brain repair is that neurons don’t regenerate after brain damage, because they don’t divide,” said Gong Chen, professor of biology and Verne M. Willaman Chair in Life Sciences at Penn State and leader of the research team. “In contrast, glial cells, which gather around damaged brain tissue, can proliferate after brain injury. I believe turning glial cells that are the neighbors of dead neurons into new neurons is the best way to restore lost neuronal functions.”
Chen’s team previously published research describing a sequence of nine small molecules that could directly convert human glial cells into neurons, but the large number of molecules and the specific sequence required for reprogramming the glial cells complicated the transition to a clinical treatment. In the current study, the team tested various numbers and combinations of molecules to identify a streamlined approach to the reprogramming of astrocytes, a type of glial cells, into neurons.
“We identified the most efficient chemical formula among the hundreds of drug combinations that we tested,” said Jiu-Chao Yin, a graduate student in biology at Pen State who identified the ideal combination of small molecules. “By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes–as many as 70 percent–into functional neurons.”
The resulting chemically converted neurons can survive more than seven months in a culture dish in the lab. They form robust neural networks and send chemical and electrical signals to each other, as normal neurons do inside the brain.
Using three of the small molecules instead of four also results in the conversion of astrocytes into neurons, but the conversion rate drops by about 20 percent. The team also tried using only one of the molecules, but this approach did not induce conversion.

A simple treatment using four small molecules converts human astrocytes – a common type of cells in the nervous system – into new neurons, which develop complex structures after four months, as pictured. NeuroscienceNews.com image is credited to Gong Chen Lab, Penn State.

Chen and his team had previously developed a gene therapy technology to convert astrocytes into functional neurons, but due to the excessive cost of gene therapy–which can cost a patient half a million dollars or more–the team has been pursuing more economical approaches to convert glial cells into neurons. The delivery system for gene therapies is also more complex, requiring the injection of viral particles into the human body, whereas the small molecules in the new method can be chemically synthesized and packaged into a pill.
“The most significant advantage of the new approach is that a pill containing small molecules could be distributed widely in the world, even reaching rural areas without advanced hospital systems,” said Chen. “My ultimate dream is to develop a simple drug delivery system, like a pill, that can help stroke and Alzheimer’s patients around the world to regenerate new neurons and restore their lost learning and memory capabilities.”
The researchers acknowledge that many technical issues still need to be resolved before a drug using small molecules could be created, including the specifics of drug packaging and delivery. They also plan to investigate potential side effects of this approach in future studies in order to develop the safest drug pills. Nonetheless, the research team is confident that this combination of molecules has promising implications for future drug therapies to treat individuals with neurological disorders.
“Our years of effort in discovering this simplified drug formula take us one step closer to reaching our dream,” said Chen.

About this neuroscience research article

Funding: This work was supported by the National Institutes of Health (AG045656), the Alzheimer’s Association (ZEN-15-321972), and the Charles H. “Skip” Smith Endowment Fund at Penn State.
In addition to Chen and Yin, other co-authors contributed to this work include Lei Zhang, Ning-Xin Ma, Yue Wang, Grace Lee, Xiao-Yi Hou, Zhuo-Fan Lei, Feng-Yu Zhang, Feng-Ping Dong and Gang-Yi Wu from Penn State.
Source: Gail McCormick – Penn State
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Gong Chen Lab, Penn State.
Original Research: Open access research for “Chemical Conversion of Human Fetal Astrocytes into Neurons through Modulation of Multiple Signaling Pathways” by Jiu-Chao Yin, Lei Zhang, Ning-Xin Ma, Yue Wang, Grace Lee, Xiao-Yi Hou, Zhuo-Fan Lei, Feng-Yu Zhang, Feng-Ping Dong, Gang-Yi Wu, and Gong Chen in Stem Cell Reports. Published February 7 2019.
doi:10.1016/j.stemcr.2019.01.003