Abstract P811: Oral Curcumin Treatment Facilitates Recovery of Function in a Rhesus Monkey Model of Cortical Injury

 Fascinating, but I'm sure this is not enough for your doctor to be able to extrapolate from Rhesus monkeys to humans. Don't do this on your own. Notice they only did male monkeys.

Abstract P811: Oral Curcumin Treatment Facilitates Recovery of Function in a Rhesus Monkey Model of Cortical Injury

 

Monica A Pessina

,

Bethany G Bowley

,

Maria Medalla

,

Douglas L Rosene

,

Tara L Moore

Originally published11 Mar 2021https://doi.org/10.1161/str.52.suppl_1.P811Stroke. 2021;52:AP811

Abstract

Curcumin is a primary component of the spice turmeric, and is a potent anti-inflammatory and anti-oxidant compound. In rodent models of brain damage from stroke or trauma, curcumin acts primarily on microglia and astrocytes to inhibit pro-inflammatory signaling pathways and to reduce inflammation and levels of reactive oxygen species (ROS). Further, rats with cortical injury treated with curcumin have smaller lesions and fewer neurological impairments than those treated with vehicle. However, it is not clear whether curcumin exerts the same biological effect in primate brains as in rodent brains, and the effects of curcumin have not yet been extensively tested in monkey models of brain injury. Data from our laboratory has demonstrated that curcumin enhances spatial working memory and motor function in normal aging rhesus monkeys given daily doses of dietary curcumin over two years. The question remains as to whether chronic dietary curcumin can enhance neuroprotection and dampen or ameliorate functional motor deficits after cortical injury. Thus, we administered curcumin to adult, male rhesus monkeys daily for two weeks prior to(So you will need pre-knowledge of when your stroke is going to occur.) and 12 weeks following induced cortical injury to the hand-representation of primary motor cortex (M1). Monkeys given daily treatment with oral doses of curcumin, but not those given vehicle, demonstrated significantly enhanced recovery of function in terms of time to retrieve a food reward on our hand dexterity task (HDT). In addition, treated monkeys returned to pre-injury finger-thumb grasp patterns on the HDT, while monkeys that received vehicle developed a compensatory whole hand grasp pattern and never returned to pre-injury grasp. These findings provide evidence that the anti-inflammatory compound, curcumin, is an effective treatment for facilitating recovery of function following cortical injury. Studies investigating the effect of curcumin on the microglia and astrocytes in the brains from these monkeys will provide evidence of the role of curcumin in reducing inflammation and ROS following injury.

Compound repairs features of Alzheimer’s disease in mice

With our quite likely chances of getting dementia/Alzheimers maybe you want your doctor to pretreat you with this. Not medical advice since I am not medically trained.
Compound repairs features of Alzheimer’s disease in mice

At a Glance

• Researchers found that a compound called an NAD+ precursor helped mice with features of Alzheimer’s disease perform better on learning and memory tests.
• The findings pave the way for studies of the compound’s potential as an intervention for people with Alzheimer’s disease.

A mouse brain showing hallmarks of Alzheimer’s disease similar to that of the mice used in this study. Abnormal protein clumps are blue, blood vessels are red, and nerve cells are green.Alvin Gogineni, Genentech

Alzheimer’s disease is a brain disorder that slowly destroys thinking, memory, and language skills. It’s the most common cause of dementia among older people. Experts estimate that more than 5 million Americans are living with the disease. Symptoms usually begin after age 60. There is no cure.

The brain’s usual DNA repair activity is impaired in Alzheimer’s disease, leading to inflammation and dysfunction. A compound that the brain needs to regulate DNA repair and other key signaling pathways is known as nicotinamide adenine dinucleotide (NAD+). Because NAD+ declines with age, scientists have wondered whether boosting the level of NAD+ could help aging brain cells (neurons) to function better. One way to increase the cellular level is by giving an NAD+ precursor compound, such as nicotinamide riboside (NR). NR is a form of vitamin B3.

An international research team led by Dr. Vilhelm A. Bohr at NIH’s National Institute on Aging (NIA) set out to test whether NR supplements could normalize NAD+ levels in the brains of mice and counteract deficits in thinking and memory. The study was published online on February 5, 2018, in the Proceedings of the National Academy of Sciences.

The research team used findings from their previous studies with human cadaver brain tissue to develop a new strain of mice. These mice had the main features of human Alzheimer’s disease, such as the abnormal buildup of the proteins tau and amyloid-beta. The research team added the NR supplement to the mice’s drinking water for three months.

The team found that the NR-treated mice had less DNA damage, lower levels of neuron damage and death, increased production of new neurons, and lower brain inflammation than control mice. Mice who received NR had reduced tau in their brains, too, but amyloid-beta levels were unchanged. The NR-treated mice performed better than control mice on many learning and memory tests, such as a water maze. In addition, NR-treated mice had better muscle strength and endurance than controls.

The research team also tested human cells from people with and without Alzheimer’s disease. As in the mouse studies, NR decreased DNA damage in the cells from people with Alzheimer’s.

“The pursuit of interventions to prevent or delay Alzheimer’s and related dementias is an important national priority,” says NIA Director Dr. Richard J. Hodes. “We are encouraging the testing of a variety of new approaches, and this study’s positive results suggest one avenue to pursue further.”

“We are encouraged by these findings that see an effect in this Alzheimer’s disease model,” Bohr says. “We are looking forward to further testing of how NR or similar compounds might be pursued for their possible therapeutic benefit for people with dementia.”

The team is continuing to study the biological mechanisms of Alzheimer’s disease in preparation for possible studies of the approach in people.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein

So when you know you are going to have a stroke get this pretreatment. Plan ahead.
http://journal.frontiersin.org/article/10.3389/fneur.2017.00256/full?

Rui-Xin Yang^1†, Jie Lei^1†, Bo-Dong Wang¹, Da-Yun Feng¹, Lu Huang¹, Yu-Qian Li¹, Tao Li², Gang Zhu¹, Chen Li¹, Fang-Fang Lu¹, Tie-Jian Nie¹, Guo-Dong Gao¹* and Li Gao¹*

• ¹Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China
• ²Research Center of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Introduction

Cerebral stroke is an important and tragic event that ranks as the second cause of death in the population. The number of incident strokes and stroke-related deaths has remained progressively increased in the past two decades (1). Cerebral stroke is defined as the sudden onset of loss of focal neurological function due to infarction or hemorrhage in the relevant part of the central nerve system, and ischemic stroke accounts for 70% of all stroke incidents (2). The best treatment for ischemic stroke is timely recanalization of the responsible artery followed by revascularization of the relevant area of the brain to salvage the peri-infarct neurons (3); however, ischemic/reperfusion (I/R) injury reduces the curative effect of this specific treatment. Therefore, to identify an efficient way to prevent I/R injury is essential for stroke patients to have a better outcome.

Cerebral I/R injury is a complex process that involves several mechanisms, including three major pathways in neurons: excitotoxicity, oxidative stress, and inflammation (4). Mitochondria play a key role in these pathways, both through ATP generation failure and as a key mediator in cell death pathways (5). In addition, I/R injury leads to mitochondrial dysfunction, which leads to oxidative stress and apoptosis (6). Thus, targeting mitochondria may be a potential therapy to reduce I/R injury.

DJ-1 is one of the causative genes associated with a familial form of Parkinson’s disease and has recently been proven to be a mitochondrial protector in I/R injury in the heart (7, 8). DJ-1 is critical for mitochondrial function, and the loss of DJ-1 causes mitochondrial fragmentation and dysfunction (9, 10). Hence, maintaining the expression and function of DJ-1 might be a promising way to protect mitochondrial function and further relieve I/R injury.

Sodium phenylbutyrate (SPB) is a small molecule (chemical structure shown in Figure 1A) that inhibits histone deacetylase activities and promotes the transcription of several genes, including that of DJ-1, in a Parkinson’s disease model (11). In this study, we investigated whether SPB exerts neuroprotection against I/R injury both in cell and animal models and explored the mechanisms underlying this protective effect.

More at link.

Intermittent hypobaric hypoxia preconditioning protects against acute severe hypoxic damage in brain

So prior to your stroke you would need to be pretreated with this. So start planning your stroke now. Or you could just live at a higher elevation. But the reduction in nitric oxide levels does not seem like a good thing.

High altitudes for Training the Brain to Survive Stroke.

Intermittent hypobaric hypoxia preconditioning protects against acute severe hypoxic damage in brain

D. Coimbra-Costa1, N. Alva1, T. Carbonell1, R. Rama1
1. Biologia cel.lular, Fisiologia i Immunologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.

Medline articles by:

• Coimbra-Costa, D
• Alva, N
• Carbonell, T
• Rama, R

---

Acute severe hypoxia (SH) causes an increase in oxidative stress and apoptosis in the brain. In contrast, intermittent hypobaric hypoxia (IHH) can increase brain antioxidant capacity and result in neuroprotection, as we previously reported (Costa et al., 2013). Thus, the present work uses IHH as preconditioning against damage potentially induced by SH. Adult rats were divided into four groups: 1) controls; 2) SH group, subjected to 6 h of acute hypoxia at 7% oxygen; 3) IHH group, exposed to 380 mmHg (equivalent to an altitude of 4000 m) in a hypobaric chamber, 4 h/day for 8 days; and 4) combined IHH-SH group, subjected to acute SH (7% oxygen) for 6 h after the last IHH exposure. Animals were anesthetized with isoflurane inhalation and then sacrificed.The brains were extracted and compared to controls.The study was approved and authorized by the Institutional Committee of Animal Care and Research of the University of Barcelona. The experimental protocol follows the European Community guidelines. SH induced oxidative stress in the brain, as indicated by increased levels of oxidized proteins, lipid peroxidation, inducible nitric oxide synthase (iNOS) expression and nitric oxide metabolites. This acute hypoxic also resulted in glutathione depletion and increased glutathione peroxidase. As for the apoptosis parameters studied, SH increased cytochrome c in the brain, and the activity of caspase 3 in the brain cortex and hippocampus. The IHH preconditioning protocol induced the expression of HIF-1 without causing oxidative stress or apoptosis, and induced expression of neuroprotective proteins such as EPO and VEGF. The IHH reduced nitric oxide levels by 28%, the content of oxidized proteins by 30% and lipid peroxidation values by 48%. It also better preserved the ratio of oxidized/reduced glutathione in brain tissue. Our study thereby demonstrates that IHH is a useful way to prepare the brain to tolerate the effects of SH better, maintaining antioxidant activity and mitochondrial function, and promoting the expression of neuroprotective factors.

Where applicable, experiments conform with Society ethical requirements

Impact of Physical Activity Before Stroke

Well, the week before my stroke I was on a whitewater canoe trip in Canada, class III+. Dog River, Ontario(23 miles and dropping 1050 feet with a 1.5 mile portage around a 120 ft. waterfall). We only portaged 5 times. 3 years post-stroke at a physical I had a resting heart rate of 54 at age 53, meaning I had the cardiovascular fitness of an athlete, even with doing no exercise for 3 years. I was in shape.

That fitness allowed me to go on a an extended wilderness canoe trip 3 years post-stroke. In 2009 this was my 'vacation'. A 21 day canoe trip on the Eagle, Bell and Porcupine rivers in the Yukon and Alaska with Wilderness Inquiry. I wouldn't call it a vacation because we paddled every day and I was quite fatigued every day. I ended up being the only disabled person on the trip.

Because of my fitness and my superior balance I take risks no survivor should try to follow.

So my read on this research is that YOUR pretreatment for stroke requires you to be very physically fit. This allows your doctor to not have to do one goddamn thing about your recovery after your stroke. Like maybe solving these  5 causes of neuronal cascade of death in the first week

Impact of Physical Activity Before Stroke

Research has suggested that people who have higher levels of physical activity before a stroke have better outcomes after the stroke has occurred, but scientists have yet to understand the underlying mechanisms.¹

Now a study has found that increased physical activity before a stroke may increase levels of vascular endothelial growth factor (VEGF). The study further found that higher levels of physical activity as well as higher levels of VEGF were linked to improved stroke outcomes and smaller infarct size. Results were published online in the Journal of Stroke and Cardiovascular Diseases.²
“In the present study we have observed that a high level of self-reported physical activity prior to stroke was associated with greater VEGF expression in the first days after ischemic stroke. Likewise, this increment in VEGF levels was independently associated with a reduction in final infarct volume and with improvement of functional outcome at 3 months,” wrote first author Elena Lopez-Cancio, MD, PhD, of the Universidad Autónoma Barcelona (UAB) (Barcelona, Spain), and colleagues.
The study was part of the AFRICA (Prestroke Physical Activity and Functional Recovery in patients with Ischemic stroke and Arterial Occlusion) study. Participants were included if they had experienced an acute ischemic event in the anterior large artery, and were admitted to a single tertiary care stroke center in Barcelona, Spain between June 2008 and January 2011.
Using a validated questionnaire, participants self-reported their physical activity in the past week before the stroke. They also provided blood samples for evaluation of circulating VEGF, granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF). Levels of these angiogenic and neurogenic factors were evaluated upon admission, at 7 days, and three months post-stroke.
The analysis included 83 patients, with a mean age of 69.6 years.
Key results:
• VEGF increased from baseline to day 7

♦ This increase was significantly higher in those with higher pre-stroke physical activity vs lower activity (mean increase 30.1 pg/mL versus 14.4 pg/mL, P<0.05)

♦ This increase was linked to significantly better NIHSS stroke severity scores at admission (−031, P=0.004) and at day 7 (−.65, P<0.001)

• Higher prestroke physical activity was linked to smaller infarct volume 30 days post-stroke and better functional outcome at 3 months
• Higher serum VEGF at day 7 was independently linked to smaller infarct volume at 30 days, and improved functional outcome at 3 months
• G-CSF and BDNF were not linked to prestroke physical activity or stroke outcomes
The authors provided several explanations for these results. Past studies have suggested that physical activity may increase VEGF expression. In turn, animal studies have suggested that VEGF may play a role in neuroprotection, neurogenesis, nitric oxide-induced angiogenesis and repair of the postischemic brain. Animals studies have also suggested that VEGF expression in parts of the brain increases after an ischemic event, and this increase has been linked to smaller infarct volume.
If VEGF is neuroprotective, administering it after stroke may improve outcomes, they suggested. Unfortunately, studies that have evaluated post-stroke VEGF delivery show positive but also negative effects, including blood-brain barrier leakage and brain edema. The authors propose that physical activity may be a safe way to increase VEGF production, rather than delivering exogenous VEGF.
“Although there are probably more molecular mechanisms by which physical activity exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed,” they concluded.
Take-home Points
• A study in Spain found that VEGF increases from baseline to day 7 in patients with ischemic stroke.
• Patients with higher levels of pre-stroke physical activity had greater increases in VEGF than those with lower levels of pre-stroke physical activity.
• Higher increases in VEGF and higher levels of pre-stroke activity were linked to improved functional outcomes at three months, and smaller infarct size at 30 days.
• Physical activity may be one way to increase synthesis of VEGF, which may be neuroprotective in stroke.
• Further studies are needed.
This study was partially supported by the Instituto de Salud Carlos III, the Spanish Research Network on Cerebrovascular Diseases, and the European Union program FEDER. Drs. Campos and Sobrino have received research contracts from Miguel Servet Program of Instituto de Salud Carlos III. Dr. López-Cancio has received a research contract from Juan Rodés program of Instituto de Salud Carlos III.

References

1. Ricciardi AC, et al. Prestroke physical activity is associated with good functional outcome and arterial recanalization after stroke due to a large vessel occlusion. Cerebrovasc Dis. 2014;37:304-311.
2. López-Cancio E, et al. Reported prestroke physical activity is associated with vascular endothelial growth factor expression and good outcomes after stroke. J Stroke Cerebrovasc Dis. 2016 Oct 28.

Injecting omega-3 fatty acid reduces brain damage in neonatal mouse model of stroke

Could our researchers correlate this research with pre and post treatment using Omega-3s? Who can take this simple task on? Or will this fall thru the cracks like every other interesting stroke study?

Looking at pretreatment with fish oil or post-treatment with fish oil

Injecting omega-3 fatty acid reduces brain damage in neonatal mouse model of stroke

Researchers from Columbia University Medical Center (CUMC) found that omega-3 fatty acids reduced brain damage in a neonatal mouse model of stroke.
Findings from the study were published recently in PLOS ONE.
The researchers treated 10-day-old mice that had incurred hypoxic-ischemic brain injury (caused by a decrease in blood flow and oxygen to the brain, as occurs during a stroke) with a fat emulsion containing either DHA or EPA--omega-3 fatty acids that are found in certain foods and in supplements. The researchers evaluated the mice's neurological function 24 hours and 8 to 9 weeks after the brain injury.
EPA and DHA are bioactive omega-3 fatty acids that are found in oils extracted from cold-water fish. The CUMC researchers and other scientists have shown that these fish-oil fatty acids protect organs and cells in numerous ways after oxygen deprivation, reducing inflammation and cell death.

At 24 hours, mice treated with DHA, but not EPA, had a significant reduction in brain injury. In the following weeks, the DHA group also had significantly better results in multiple brain functions compared to the EPA-treated mice and untreated (control) mice.
The researchers also discovered that these mice had increased concentrations of DHA in their brain mitochondria, energy-producing structures in cells that can be injured by free radicals when blood flow is restored to the brain after a stroke. This process, known as reperfusion injury, is a common cause of brain damage following the oxygen and nutrient deprivation that occurs after a stroke.
"Our findings suggest that injecting the omega-3 fatty acid DHA after a stroke-like event has the ability to protect brain mitochondria against the damaging effects of free radicals," said senior co-author, Vadim S. Ten, MD, PhD, associate professor of pediatrics at CUMC.
Interruption of blood flow and oxygen supply to the brain during or shortly after birth is a major cause of brain damage in newborns, causing life-long neurological impairments in more than 25 percent of those affected. Many of the pathways involved in this type of brain damage are similar to those in an adult stroke.
"Clinical trials are needed to determine if administering lipid emulsions containing DHA shortly after a stroke-like brain injury offers the same neuroprotective effects in babies and adults, as seen in mice. If successful, such trials could lead to the development of a novel therapy for stroke in newborns, children, and adults, addressing a major medical need," said senior co-author Richard J. Deckelbaum, MD, CM, the Robert R. Williams Professor of Nutrition (in Pediatrics) and Professor of Epidemiology and director of the Institute of Nutrition at CUMC.

Source:

Columbia University Medical Center

Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice

You'll have to ask your doctor how much red wine is needed for this pretreatment and the length of time it needs to be applied to have the best effect. Not to be done on your own. Being a male I will have to totally guess the amounts and hope it works the same way. I'd  be willing to bet that this pretreatment should start even while you are in the hospital. It is a twofer, you get pretreatment and challenging balance tasks allowing you to recover your balance faster. Why hasn't your doctor come to these same obvious conclusions?

Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice

Sae Im Jeong

,

Jin A. Shin

,

Sunghee Cho

,

Hye Won Kim

,

Ji Yoon Lee

,

Jihee Lee Kang

,

Eun-Mi ParkPress enter key for correspondence informationPress enter key to Email the author

DOI: http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.007

Abstract

Resveratrol is known to improve metabolic dysfunction associated with obesity. Visceral obesity is a sign of aging and is considered a risk factor for ischemic stroke. In this study, we investigated the effects of resveratrol on inflammation in visceral adipose tissue and the brain and its effects on ischemic brain injury in aged female mice. Mice treated with resveratrol (0.1 mg/kg, p.o.) for 10 days showed reduced levels of interleukin-1β and tumor necrosis factor-α, as well as a reduction in the size of adipocytes in visceral adipose tissue. Resveratrol also reduced interleukin-1β and tumor necrosis factor-α protein levels and immunoglobulin G extravasation in the brain. Mice treated with resveratrol demonstrated smaller infarct size, improved neurological function, and blunted peripheral inflammation at 3 days postischemic stroke. These results showed that resveratrol counteracted inflammation in visceral adipose tissue and in the brain and reduced stroke-induced brain injury and peripheral inflammation in aged female mice. Therefore, resveratrol administration can be a valuable strategy for the prevention of age-associated and disease-provoked inflammation in postmenopausal women.

Keywords:

Aging, Females, Inflammation, Ischemic stroke, Resveratrol, Visceral adipose tissue

Black sugarcane decoction reduces rat brain ischemia

Further research would be needed to see if this delivered in the hyperacute stage would reduce ischemia. But that will never occur, we have NO fucking stroke leadership or strategy.

http://www.univmed.org/ejurnal/index.php/medicina/article/view/142 
 

ety sari handayani, zainuri sabta nugraha, Titis Nurmasitoh, Kuswati Kuswati, Dwi N. Ahsani, Ajeng G. Nanda

Abstract

Background
There are people in Yogyakarta, who use black sugarcane decoction (BSD) to prevent stroke. BSD contains policosanol and antioxidants. It has been proven that policosanol can reduce global ischemia in Mongolian gerbils. This study aims to evaluate the effect of BSD on brain ischemia in a rat stroke model.

Methods
A laboratory experiment using eighteen 3-month old male Wistar rats without any defects, of 175-250 g body weight. Brain ischemia was produced by a 20-minute bilateral carotid artery ligation (BCAL). Using a rat stroke model, brain ischemia was produced by a 20-minute bilateral carotid artery ligation (BCAL). The rats were randomized into three groups: BSD treated stroke model rats (group 1), non treated stroke model rats (group 2), and sham operated rats (group 3). BSD was administered by gavage for 1 week before BCAL. Decapitation of rats was performed two hours post BCAL. Brain tissues were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Ischemic areas were analyzed using Image J softwere. Statistical analysis was conducted by one way ANOVA test.

Results
The mean percentages of rat brain ischemic area differed between group 3 (0.0 ± 0.0 %), group 2 (3.13 ± 0.59 %) and group 1 (1.15 ± 0.47 %) p =0.001). Post hoc test showed that there was no difference between group 3 with group 1. Instead, there was a significant difference between group 2 and the other groups.

Conclusion
The administration of BSD reduced rat brain ischemia after bilateral carotid artery ligation.

Tailored new compound can dramatically reduce brain damage resulting from stroke - hydrogen sulfide inhibition

Now if we had ANY stroke leadership at all we would propose and start research trials in humans. But we don't so we are screwed for at least another 50 years. And if you know you are going to have a stroke you could get pretreatment. Maybe if your are having surgery for an AVM or aneurysm and are worried about having a stroke during surgery. This is not medical advice, ask your doctor these simple questions
http://www.news-medical.net/news/20160310/Tailored-new-compound-can-dramatically-reduce-brain-damage-resulting-from-stroke.aspx 

After suffering a stroke, about three-fourths of patients exhibit some disability. The extent of a patient's symptoms depends on the degree and location of brain tissue damage following the stroke event. This week in ACS Central Science, researchers show that by using a tailored small molecule to turn off the production of a key neuromodulator in the brain, they can dramatically reduce brain damage in stroke models in rats.
The neuromodulator is the gas hydrogen sulfide (H2S). Its production is carefully controlled in the brain. After a stroke, levels of H2S appear to be elevated, leading to brain tissue damage, but the details of how that happens are still a bit of a mystery. So, David B. Berkowitz and coworkers designed a quick way to synthesize molecules they deduced would inhibit the production of H2S. They showed in vitro that these compounds block an enzyme called CBS from making H2S by mimicking one of its other products. Peter T. H. Wong and colleagues then tested the compounds in rats. When the new compound was injected an hour after the simulation of a stroke, the authors observed about a 70 percent reduction in the severity of the observed stroke damage. The results were even more striking with pretreatment. The authors conclude that using molecules like the ones they made will help researchers dissect the mechanism underlying H2S-mediated neuronal damage and will serve as an important starting point for the development of even more drug-like compounds that act in a similar manner.

Source:

American Chemical Society

Our stroke leaders should be following this closely to see what can be used in stroke. Or at a minimum create a similar roundtable for stroke. But NOTHING will occur. I wonder if there will be anything on:

Looking at pretreatment with fish oil or post-treatment with fish oil

FOR IMMEDIATE RELEASEMarch 9, 2016

CONTACT: Press Office(202) 226-4972

Committee Announces Distinguished Lineup of Experts for Concussion Roundtable

 

Participants Include Representatives of Medical, Military, Athletic, and Research Communities for Discussion @ 2PM on Monday, March 14

WASHINGTON, DC – The House Energy and Commerce Committee’s broad review of concussions will commence next week with a roundtable discussion about the state of our knowledge concerning the causes, effects, and treatments of concussions and head trauma. The discussion, which will feature input from experts representing the medical, military, athletic, and research communities, is focused on building a collaborative body of knowledge to help improve the diagnosis and treatments of concussions. The roundtable, entitled, “Broad Review on Concussions: Initial Roundtable,” will take place at 2 PM on Monday, March 14. A webcast and additional information will be available HERE.

“There are no easy answers or simple solutions when it comes to head injuries. The goal of our roundtable is to advance the conversation beyond the attention-grabbing headlines to make a real difference for individuals across the country by bringing together experts on head trauma including the public health, military, athletic, and research communities. We’ll explore what we know and don’t know about concussions, and how the research community is working to meet these challenges. At the end of the day, we want to identify opportunities to achieve meaningful progress in our ability to diagnose and treat concussions,” said Energy and Commerce Committee Chairman Fred Upton (R-MI), and Oversight and Investigations Subcommittee Chairman Tim Murphy (R-PA). Murphy will be leading Monday’s discussion.

QUESTIONS FOR DISCUSSION
The committee has posed the following questions to help guide Monday’s roundtable discussion:

• What are the most prominent misconceptions or underappreciated facts about concussions?
• What are the critical gaps in our understanding of concussions? Why do these gaps exist? How do these knowledge gaps hinder progress in minimizing the risks of concussions?
• What are the most critical short and long-term objectives if we hope to achieve meaningful progress minimizing the risks of concussions?
• What, if any, coordination exists or is needed to ensure that independent research efforts contribute to short and long term objectives?

PARTICIPANTS
Dr. Grant Baldwin - Director of the Division of Unintentional Injury Prevention at the National Center for Injury Prevention, Centers for Disease Control and Prevention 

Dr. David Cifu - Herman J. Flax, M.D. Professor and Chairman, Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University. Principal Investigator for the VA/DoD Chronic Effects of Neurotrauma Consortium (CENC) 

Dr. Michael (Micky) Collins - Director of Sports Medicine Concussion Program, University of Pittsburgh Medical Center

Capt. (Dr.) Michael Colston – Director, Defense Center of Excellence for Psychological Health and Traumatic Brain Injury, Department of Defense  

Dr. Gerald Gioia - Division Chief of Neuropsychology and Director of the Safe Concussion Outcome, Recovery & Education (SCORE) Program, Children's National Health System; and Professor at George Washington University School of Medicine 

Col. Dallas Hack (ret.) - Consultant – Directed the DoD Combat Casualty Care Research Program from 2008-2014 (currently consulting a number of organizations, including the NCAA and OneMind, to advance research in Brain Health and transition the progress to improved clinical practice) 

Dr. Brian Hainline - Chief Medical Officer, National Collegiate Athletic Association 

Dr. Walter Koroshetz - Director of National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health 

Dr. Geoff Manley - Chief of Neurosurgery at San Francisco General Hospital and Professor of Neurosurgery at University of California San Francisco (Contact Principal Investigator for large international TBI research initiative, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI)) 

Dr. Michael McCrea - Professor of Neurosurgery and Neurology, and Director of Brain Injury Research, University of Wisconsin

Ms. Lisa McHale – Director of Family Relations, Concussion Legacy Foundation

Dr. Anne McKee – Professor of Neurology & Pathology, Director, Neuropathology Core, Alzheimer’s Disease Center, Boston University

Mr. Jeff Miller – Senior Vice President of Health and Safety Policy, National Football League

Stroke Rounds: Statin Users Have Better Outcomes

But they didn't compare it to these other pretreatment options. So as far as research is concerned this is pretty worthless. Damn it all,  does no one in stroke ever think at all? Do they not know about this other research?

High altitudes for Training the Brain to Survive Stroke.

 

Neurovascular Mechanisms of Ischemia Tolerance Against Brain Injury

 

Prior Cannabis Use Is Associated with better Outcome after Intracerebral Hemorrhage

 

Vaccine shows potential to protect the brain before a stroke

 

Mice were pretreated with genistein (2.5, 5, and 10mg/kg) or vehicle orally once daily for 14 consecutive days before MCA.

  

Numerous reports of lower in-hospital mortality among smokers versus nonsmokers 

Clinically established low doses of memantine should be considered for patients 'at risk' of stroke 

 

Pretreatment of fish oil supplementation in a rat model of multiple mild traumatic brain injuries.  

And the fairly worthless one-off here:

Stroke Rounds: Statin Users Have Better Outcomes

Preexisting statin use was associated with better outcomes in patients with acute ischemic stroke (AIS) from large artery atherosclerosis (LAA), an international, multicenter study showed.
Neurologic improvement during hospitalization was greater in patients on a statin and taking it in the days prior to stroke than in those not taking a statin (66.7% versus 38.9%; P=0.004), Georgios Tsivgoulis, MD, PhD, of the University of Tennessee Health Science Center in Memphis, and colleagues found.
Statin use before stroke was independently associated with favorable functional outcome using a modified Rankin Scale (mRS) score of 0-1 (odds ratio 2.44%; 95% confidence interval 1.07-5.53), the investigators reported online in Neurology.
Patients with LAA who received statins prior to the onset of AIS also had a lower risk of stroke recurrence (hazard ratio 0.11; 95% CI 0.02-0.46) at 30 days and a lower risk of 1-month mortality (HR 0.24; 95% CI: 0.08-0.75), the study showed.
"Our findings provide preliminary observational evidence underscoring a potentially beneficial effect of statins in improving early stroke outcomes in AIS patients with an underlying atherothrombotic mechanism," the researchers wrote. "This hypothesis deserves to be further tested in the setting of a randomized controlled trial."
Results from this study lend support to current American Heart Association/American Stroke Association recommendations for continuation of statin treatment during the acute period in pretreated AIS patients, pointed out the investigators. However, they emphasized, in the absence of phase III, randomized controlled trial data on the safety and efficacy of statins during the first 30 days following stroke, the observational study design and the short follow-up "does not allow us to infer any causal associations between statin pretreatment and improved outcomes in patients with acute LAA."
While this study provides "key data" and adds to the growing evidence about the benefits of statin use in AIA, "the results should be interpreted with caution because of potential residual confounding," Andreas Charidimou, MD, PhD, of the Massachusetts General Hospital Stroke Research Center in Boston, and Áine Merwick, MB, PhD, of the Westminster NHS Foundation Trust in London, cautioned in an accompanying editorial.
"Unlike strong evidence supporting statin use in cardiovascular risk reduction and acute myocardial ischemia, their effects on cerebral tissue and potential benefits on stroke outcomes remain poorly understood and under-studied," said the editorialists. "The only current stroke-specific indication for statin use is atorvastatin (Lipitor) for secondary stroke prevention," they noted.
Charidimou and Merwick agreed on "the urgent need for a large randomized clinical trial of high-dose statin treatment in the acute stroke setting."
Statin pretreatment may play a role in symptomatic and asymptomatic patients undergoing carotid endarterectomy as well as in the periprocedural and postprocedural outcomes of patients undergoing carotid artery stenting procedures, they pointed out. In addition, data from this study may have implications for the management of asymptomatic carotid disease as well as interpretive value for ongoing studies such as the European Carotid Surgery Trial 2, said Charidimou and Merwick.
Tsivgoulis' study prospectively evaluated 516 consecutive first-ever AIS patients with LAA from seven tertiary stroke care centers from June 2011 to June 2014. The mean age was 65 years and 60.8% were male. The median NIHSS score was 9 points. LAA was diagnosed by TOAST criteria.
Statin pretreatment was documented in 192 (37.2%) patients. Information on the duration, dosage, and type of prestroke statin therapy was not collected, the authors noted.

Prior Cannabis Use Is Associated with better Outcome after Intracerebral Hemorrhage

Well, see what your doctor has to say about this pretreatment for stroke with cannabis. Although this is correlation not cause. Tweak your doctor anyway about this. Or is the better result because these were young patients? Doesn't anyone in stroke understand cause and effect?
http://www.karger.com/Article/Abstract/443532
Di Napoli M.^{a, b} · Zha A.M.^c · Godoy D.A.^{d, e} · Masotti L.^f · Schreuder F.H.B.M.^g · Popa-Wagner A.^{h, i} · Behrouz R.^j · from the MNEMONICH Registry
^aNeurological Service, San Camillo de' Lellis General Hospital, Rieti, ^bNeurological Section, SMDN - Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L'Aquila, Italy; ^cDepartment of Neurology, Ohio State University College of Medicine, Columbus, Ohio, USA; ^dThe Neurointensive Care Unit, Sanatorio Pasteur and ^eIntensive Care Unit, Hospital Interzonal de Agudos ‘San Juan Bautista', Catamarca, Argentina; ^fDepartment of Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy; ^gDepartment of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands; ^hDepartment of Psychiatry, Rostock University Medical School, Rostock, Germany; ⁱUniversity of Medicine and Pharmacy, Craiova, Romania; ^jDepartment of Neurology, School of Medicine, University of Texas Health Science Center San Antonio, San Antonio, Tex., USA

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Abstract

Objective: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke(not proven). The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients.  
Methods: An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores.  
Results: Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB⁺) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB⁺ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). Conclusion: In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB⁺ patients had milder ICH presentation and less disability at discharge.

Vaccine shows potential to protect the brain before a stroke

This should be added to other pretreatment possibilities: 

1.  Pretreated with genistein

2.  Numerous reports of lower in-hospital mortality among smokers versus nonsmokers 
3.  Clinically established low doses of memantine should be considered for patients 'at risk' of stroke
4.  Effect of fish oil supplementation in a rat model of multiple mild traumatic brain injuries

5. Warfarin Pretreatment Reduces Cell Death and MMP-9 Activity in Experimental Intracerebral Hemorrhage
6.  High Altitudes - Training the Brain to Survive Stroke

Vaccine shows potential to protect the brain before a stroke

A type of vaccine previously studied to treat high blood pressure may have the potential to protect the brain when administered before a stroke, according to an animal study presented at the American Stroke Association’s International Stroke Conference 2016.
Japanese researchers tested a peptide vaccine targeting the hormone angiotensin II (Ang II) a key player in high blood pressure. Members of the research team previously had found that their peptide vaccine decreased blood pressure in a mouse model of hypertension, while the blood pressure of mice with normal readings was unaffected. The hormone also has been linked to patients’ prognosis after a ischemic (clot-caused) stroke.
In the new study, researchers injected 53 male rats with the vaccine three times, at ages 4, 6 and 7 weeks old, and administered a second group of 41 with saline at the same intervals. Stroke was induced in vaccinated rats and rats that were given saline.
The team then measured levels of anti-Ang II antibody in the blood and brains of the rats that received the vaccine and had a stroke. Compared with rats that had low blood levels of antibody, the animals with high levels in the blood had more anti-Ang II antibodies in functional tissue at the side of the brain where the stroke occurred. Researchers also noted that vaccinated rats that produced high blood levels of antibody had less damage to the brain and fewer degenerated neurons.
Because the Ang II peptide vaccine is long-lasting, has anti-inflammatory effects and appears able to protect the brain after a blood vessel blockage, it has potential to be a therapy for high blood pressure and stroke prevention, researchers said.

http://newsroom.heart.org/news/basic-science-tip-sheet-3127213?preview=288bf38a9020a77868a1001b3426486c

• Full bibliographic informationPoster T P269 - Kouji Wakayama, Univ of Tokyo, Tokyo, Japan; Munehisa Shimamura, Osaka Univ, Osaka, Japan; Jun-ichi Suzuki, Univ of Tokyo, Tokyo, Japan; Mitsuaki Isobe, Tokyo Medical and Dental Univ, Tokyo, Japan; Hironori Nakagami, Ryuichi Morishita, Osaka Univ, Osaka, Japan
  Therapeutic Application of an Angiotensin II Peptide Vaccine in a Middle Cerebral Artery Occlusion Model in Rats.
  American Heart Association’s International Stroke Conference 2016, February 16-19, 2016, Los Angeles, California.

Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model

Only three years old and I bet your doctor and hospital have not done one fucking thing to help your recovery based upon this research. What is the downside even though this is only in mice? Are your doctors waiting for clinical human studies before they do anything? Stroke survivors will never get better if we don't have any doctors willing to show some initiative and try new stuff based upon research. They can have you sign a waiver stating you won't sue them for feeding you soybeans. So much that can be done for survivors and no one even trying to help them. And you wonder why I'm angry all the time. I fucking hate stupid people. Lazy people even more.
But this might be difficult because you have to know 14 days before your stroke so you can start pretreatment. This would then require research showing if this is helpful treating poststroke. So much research to do and no one to do it.
http://www.ncbi.nlm.nih.gov/m/pubmed/22490611/?i=6&from=soy%20stroke

Qian Y, et al. Neurochem Int. 2012.

Show full citation

Abstract

Recently, the treatment of stroke has focused on antioxidant therapies, where oxidative stress is implicated. The preventive and therapeutic potential of plant compounds on ischemic stroke has been intensively studied because many of them contain antioxidant properties. Genistein, one of the active ingredients in soybean, possesses many bioactivities. In this study, we investigated the potential neuroprotective effects of genistein and its possible mechanism of action in a cerebral ischemia mouse model. Mice were pretreated with genistein (2.5, 5, and 10mg/kg) or vehicle orally once daily for 14 consecutive days before transient middle cerebral artery occlusion was performed. Genistein at doses of 2.5-10mg/kg significantly reduced the infarct volume, improved the neurological deficit and prevented cell apoptosis after ischemia. In addition, genistein pretreatment was shown to inhibit the ischemia-induced reactive oxygen species (ROS) production, enhance the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and decrease levels of malondialdehyde (MDA) in stroke mice. Moreover, genistein reversed the mitochondria dysfunction after ischemia, as evidenced by decreasing mitochondria ROS levels, preventing cytochrome C release to the cytoplasm and inhibiting caspase-3 activation. Western blotting showed ischemia activated the ROS-dependent nuclear factor-κB (NF-κB) signaling pathway, and genistein suppressed phosphorylation and activation of the NF-κB p65 subunit, as well as the phosphorylation and degradation of the inhibitor protein of κBα (IκBα). Our findings suggested that genistein has a neuroprotective effect in transient focal ischemia, which may involve regulation of mitochondria-dependent apoptosis pathways and suppression of ROS-induced NF-κB activation.

Smoking Paradox in Patients Hospitalized With Coronary Artery Disease or Acute Ischemic Stroke

Maybe because nicotine has some pretreatment effect? Better neural connections? More brain reserve? Don't start smoking because of this. I'm sure your doctor has no fucking clue about this.

Chronic nicotine restores normal Aβ levels and prevents short-term memory and E-LTP impairment in Aβ rat model of Alzheimer's disease

 Smoking Paradox in Patients Hospitalized With Coronary Artery Disease or Acute Ischemic Stroke

1. Syed F. Ali, MD,
2. Eric E. Smith, MD, MPH,
3. Mathew J. Reeves, PhD,
4. Xin Zhao, MS,
5. Ying Xian, MD, PhD,
6. Adrian F. Hernandez, MD, MHS,
7. Deepak L. Bhatt, MD, MPH,
8. Gregg C. Fonarow, MD and
9. Lee H. Schwamm, MD

+ Author Affiliations

1. From the Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston (S.F.A., L.H.S.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Duke Clinical Research Institute, Durham, NC (X.Z., Y.X., A.F.H.); Division of Cardiology, Brigham and Women’s Hospital Heart and Vascular Institute, Boston, MA (D.L.B.); Harvard Medical School, Boston, MA (D.L.B.); and Division of Cardiology, Ronald Reagan-UCLA Medical Center (G.C.F.).

1. Correspondence to Lee H. Schwamm, MD, Department of Neurology, ACC 720, Massachusetts General Hospital, Boston, MA 02114. E-mail lschwamm@partners.org

Abstract

Background—Smoking is a potent risk factor for coronary artery disease (CAD) and acute ischemic stroke (AIS), but there are numerous reports of lower in-hospital mortality among smokers versus nonsmokers hospitalized for these events.

Methods and Results—We analyzed all consecutive patients hospitalized with a first index CAD (n=158 054) or AIS (n=899 295) event in Get With The Guidelines from 2002 to 2012; 20.4% of AIS and 30.4% of patients with CAD were past-year smokers. Multivariable models and age-stratified analyses were used to estimate the adjusted odds ratio of in-hospital mortality in smokers versus nonsmokers. Smokers were younger, more often male, with fewer vascular risk factors, and were more likely to be admitted to hospitals that were large, academic, or in the South. In-hospital mortality was significantly lower among smokers in both CAD (2.7% versus 5.2%; P<0.0001) and AIS (3.5% versus 5.8%; P<0.0001). The difference between unadjusted and adjusted odds ratios for smoking (0.57 versus 0.86 in CAD; 0.56 versus 0.86 in AIS) indicates the presence of substantial confounding by age and other covariates, but a significant association of past-year smoking remained.

Conclusions—Among patients hospitalized with CAD and AIS, smoking is a risk factor for early age of onset, even among those with few vascular risk factors. The persistent association with lower in-hospital mortality after adjusted and stratified analyses probably represents residual unmeasured confounding, although a biological effect of smoking cannot be excluded. Further clinical and prospective population-based studies are needed to explore variables that contribute to outcomes in these patients.