Low-intensity preconditioning boosts neurological outcomes

Your competent? doctor will need to EXACTLY PREDICT YOUR NEXT STROKE within four weeks so you can do this preconditioning. 

Low-intensity preconditioning boosts neurological outcomes

The team led by Prof. Lin Zhu from Guangzhou Sport University have demonstrated that 4-week low-intensity treadmill exercise before the onset of an ischemic stroke can significantly reduce brain injury and improve neurological outcomes.

This study, published in Translational Exercise Biomedicine (ISSN: 2942-6812), an official partner journal of International Federation of Sports Medicine (FIMS), offers a promising, non-pharmacological strategy for the millions of people worldwide at risk of this debilitating condition.

Ischemic stroke, caused by a blockage in blood flow to the brain, remains a leading cause of death and long-term disability worldwide. Although treatments like thrombolysis are available, narrow time windows significantly limit their therapeutic effects. This has led scientists to explore proactive, preventive measures against stroke.

The research team investigated the concept of exercise preconditioning using regular physical activity to build the brain's resilience against a future injury. The study focused on low-intensity exercise, more accessible and sustainable for at-risk populations, particularly the elderly.

Our study provides robust evidence that even low-intensity exercise can precondition the brain to be more resistant to the devastating effects of an ischemic stroke. The beauty of this approach is its practicality, it doesn't require strenuous activity, making it a viable strategy for older adults or those with physical limitations or at risk of stroke."

Lin Zhu, Study Team Leader and Professor, Shanghai Jiao Tong University

The researchers established a transient middle cerebral artery occlusion (tMCAO) mouse model, the standard for simulating human ischemic stroke. Twelve-week-old male mice were divided into three groups: healthy control group (Sham), stroke group (tMCAO), and exercise preconditioning group (Ex+tMCAO) that underwent four weeks of low-intensity treadmill running, 10 m/min for one hour a day, five days a week, before the stroke was induced.

The results were striking. At 24 hours after the stroke, the mice that had exercised showed significantly reduced infarct size. Brain tissue death was markedly lower compared to the non-exercised stroke group. In addition, the exercised mice exhibited a higher density of CD31-positive microvessels, indicating improved formation of new blood vessels in the brain, which is crucial for recovery and supplying oxygen to stressed tissues.

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Exercise preconditioning also dramatically reduced the apoptosis in neurons. At the molecular level, the exercised mice showed significantly lower expression of key pro-inflammatory cytokines and chemokines in the brain, including IL-6, CCL11, CCL2, CXCL1, and Fosl1. These factors are known to exacerbate brain damage by recruiting immune cells and triggering harmful inflammatory cascades. While the exercise group showed a trend toward improved performance on motor coordination tests, like the rotarod test, the improvements were not statistically significant at the 24-hour mark, suggesting that while tissue damage is reduced, functional recovery may take a longer period of time.

Co-corresponding author Prof. Xiaoguang Liu added, "We were excited to see the down-regulation of multiple inflammatory pathways. This confirms that exercise preconditioning not only just act through one mechanism, but also creates a broad, protective environment in the brain by simultaneously boosting repair mechanisms like angiogenesis and suppressing inflammation and apoptosis."

However, the authors acknowledge several limitations. The study was conducted only using young male mice, and female and aged models are needed to validate the results. Furthermore, though gene expression for inflammatory markers was measured, protein-level confirmation is needed to confirm the mechanistic conclusions. 

Despite these limitations, the findings have profound implications for public health. They suggest that encouraging regular, gentle physical activity, such as a brisk walk, could serve as an effective, low-cost preventive medicine against stroke.

This is especially relevant given the rising incidence of stroke in younger adults and the aging global population. Besides, this study also has certain translational significance. Building a "brain reserve" through consistent, manageable exercise could be one of the most effective ways to reduce global burden of ischemic stroke. It transforms the concept of exercise from a rehabilitative tool to a powerful preemptive exercise medicine.

Source:

Shanghai Jiao Tong University

Journal reference:

Chen, P., et al. (2026). Low-intensity treadmill exercise preconditioning alleviates post-ischemic stroke injury in mice by inhibiting ischemia-induced inflammation and apoptosis. Translational Exercise Biomedicine. DOI: 10.1515/teb-2025-0029. https://www.degruyterbrill.com/document/doi/10.1515/teb-2025-0029/html.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS

 Didn't your competent? doctor figure out a protocol on this 5 years ago? NO? So you DON'T have a functioning stroke doctor? Why are you seeing them?

• endothelial nitric oxide (1 post to January 2019)

I guess a major problem with this it has to be performed before your stroke. You'll need time travel or precognitive dreams about your upcoming stroke.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS

eNOS

Shinya Yokomizo,

Timo Kopp,

Malte Roessing,

Atsuyo Morita,

Seeun Lee,

Suin Cho,

Emiyu Ogawa,

Eri Komai,

Kazumasa Inoue,

Masahiro Fukushi,

Susanne Feil,

Hyung-Hwan Kim,

Denis E. Bragin,

… See all authors

Originally published4 Apr 2024https://doi.org/10.1161/STROKEAHA.123.045358Stroke. 2024;0

Abstract

BACKGROUND:

The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury.

METHODS:

This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits.

RESULTS:

Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm² improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes.

CONCLUSIONS:

Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.

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Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis

 Evidence seems to suggest having a TIA means your subsequent stroke might be lighter. I highly doubt you could construct clinical human research on this. Lets give you a TIA and then a see if your subsequent stroke is less damaging.

Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis

Sherief Ghozy^1*†, Salah Eddine Oussama Kacimi^2†, Mohammed Elfil^3†, Mohamed Gomaa Sobeeh^4,5, Abdullah Reda⁶, Kevin M. Kallmes^7,8, Alejandro A. Rabinstein⁹, David R. Holmes Jr.¹⁰, Waleed Brinjikji^1,11, Ramanathan Kadirvel¹ and David F. Kallmes¹

• ¹Department of Radiology, Mayo Clinic, Rochester, MN, United States
• ²Faculty of Medicine, University of Tlemcen, Tlemcen, Algeria
• ³Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States
• ⁴Faculty of Physical Therapy, Cairo University, Cairo, Egypt
• ⁵Faculty of Physical Therapy, Sinai University, Cairo, Egypt
• ⁶Faculty of Medicine, Al-Azhar University, Cairo, Egypt
• ⁷Nested Knowledge, St. Paul, MN, United States
• ⁸Superior Medical Experts, St. Paul, MN, United States
• ⁹Department of Neurology and Neurocritical Care, Mayo Clinic, Rochester, MN, United States
• ¹⁰Department of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN, United States
• ¹¹Department of Neurosurgery, Mayo Clinic Rochester, Rochester, MN, United States

Stroke is a leading cause of mortality and disability worldwide. Transient ischemic attack (TIA) is defined as transient brain ischemia with temporary neurological deficits. In animal models, prior TIA seems to enhance brain ischemic tolerance to withstand further ischemic events, which might be explained by brain preconditioning. Thus, this review aims to formulate evidence of whether TIAs can induce positive preconditioning and enhance the functional outcomes in patients suffering from subsequent ischemic strokes. Five databases were searched (PubMed, Embase, SAGE, Web of Science, and Scopus), and twelve studies were included in the quantitative analysis. Studies were eligible when comparing patients with acute ischemic stroke (AIS) and previous TIA with those with AIS without TIA. Comparisons included the National Institute of Health Stroke Scale (NIHSS) score at admission and 7 days from the stroke event, modified Rankin score (mRS), and Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to describe our results using the random effect model. Our results revealed that patients with stroke and prior TIAs had lower NIHSS scores at admission than those without prior TIAs. However, the NIHSS score was not significantly different between the two groups at 7 days. Furthermore, there was no statistically significant difference between both groups in terms of mortality. Despite the differences in the admission mRS score groups, patients with prior TIAs had lower mRS scores at discharge.

Introduction

Stroke is one of the most common causes responsible for mortality, morbidity, and loss of function worldwide (1). Furthermore, it has been reported that after the age of 55, the risk of having stroke doubles per each subsequent decade, with overburdened healthcare economics for these patients (2). Consequently, many management approaches have been extensively reported in the literature, which mainly target decreasing the incidence of severe events and mortality after a stroke event, in addition to enhancing recovery and rehabilitation among the survivors (3–6).

Although ischemia accounts for a significant part of brain tissue injury during stroke, reperfusion also contributes to brain tissue damage (7). Many explanations have been proposed to explain the underlying pathophysiology of the reperfusion injury, including the potential dysregulation of the intracellular calcium (8), impaired ion transport across the plasma membrane (8, 9), and increased synthesis and release of pro-inflammatory cytokines and reactive oxygen species (10, 11), all of which can cumulatively lead to the opening of the mitochondrial permeability transition pores resulting into tissue necrosis (12, 13). Thus, many approaches have been suggested to regulate the process of ischemia-reperfusion and enhance the clinical and prognostic outcomes. Ischemic preconditioning (IPC) has shown a potential as a modality in reducing the severity of the post-ischemic events. However, controversies still exist in literature about the potential neuroprotective effects that this approach might have (14).

Ischemic tolerance has been primarily described in experimental studies as a process during which the brain is subjected to a short period of ischemia which might enable the brain to be more tolerant when exposed to a more persistent ischemic event (15–19). Therefore, it has been proposed that pre-stroke exposure to Transient ischemic attacks (TIAs) might have a potential neuroprotective role when persistent ischemia affects the same exposed region. However, clinical studies reported contradicting findings regarding the ability of TIAs to alleviate the severity of cerebral ischemic injury (20–23). Accordingly, we aimed to conduct this systematic review and meta-analysis to formulate evidence whether TIAs can induce positive brain preconditioning and enhance the functional outcomes in patients suffering from subsequent AIS.

More at link.

 

 

 

REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in Catalonia: REMOTE-CAT PROJECT

 Well fuck three different methods have had research out there for years.  You'll have to ask your doctor the difference between perconditioning and preconditioning.

If your stroke hospital has done nothing with any.

• leg compressions (13 posts to August 2012)

• leg wraps (5 posts to May 2013)

• External counterpulsation (4 posts to August 2013)  

NOTHING?

Then get that doctor, the stroke department head, the president and the board of directors fired. FOR INCOMPETENCE!

The latest here:

REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in Catalonia: REMOTE-CAT PROJECT

Francisco Purroy^1,2*†, Gloria Arque^2†, Gerard Mauri^1,2, Cristina García-Vázquez², Mikel Vicente-Pascual^1,2, Cristina Pereira², Daniel Vazquez-Justes^1,2, Coral Torres-Querol², Ana Vena^1,2, Sònia Abilleira³, Pere Cardona⁴, Carles Forné^5†, Xavier Jiménez-Fàbrega⁶, Jorge Pagola⁷, Manuel Portero-Otin⁸, Ana Rodríguez-Campello⁹, Àlex Rovira¹⁰ and Joan Martí-Fàbregas¹¹

• ¹Stroke Unit, Department of Neurology, Hospital Universitari Arnau de Vilanova de Lleida, Lleida, Spain
• ²Clinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), Universitat de Lleida, Lleida, Spain
• ³Stroke Programme, Agency for Health Quality and Assessment of Catalonia, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
• ⁴Stroke Unit, Hospital de Bellvitge, Hospitalet de Llobregat, Spain
• ⁵Department of Basic Medical Sciences, Universitat de Lleida, Lleida, Spain
• ⁶Servei d'Emergències Mèdiques, Hospitalet de Llobregat, Spain
• ⁷Stroke Unit, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain
• ⁸Department of Experimental Medicine, NUTREN-Nutrigenomics, Biomedical Institut de Recerca Biomèdica de Lleida (IRBLleida), Universitat de Lleida, Lleida, Spain
• ⁹Neurovascular Research Group, Neurology Department, Institut Hospital del Mar d'Investigacions Mèdiques-Hospital del Mar, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
• ¹⁰Section of Neuroradiology and MRI Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
• ¹¹Stroke Unit, Hospital de Sant Pau, Barcelona, Spain

Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection.

Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care.

Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%.

Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device.

Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days.

Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03375762.

Introduction and Rationale

Stroke is one of the leading causes of death worldwide and the main cause of disability (1). Currently, the only therapies for acute ischemic stroke (AIS) patients are the administration of rt-PA (2) and/or endovascular treatment (3). Unfortunately, many patients cannot benefit from these therapies due to their contraindications or evolution time. Neuroprotective therapies could not only increase the benefits of available reperfusion therapies but also provide an option for patients who are not candidates for these treatments (4). However, most neuroprotection trials have so far failed to demonstrate their efficacy in AIS patients, despite promising results in animal studies (4). Remote ischemic perconditioning (RIPerC) represents a new paradigm in neuroprotection (5). It potential upregulates endogenous defense systems to achieve ischemic tolerance in brain ischemia (6). It consists of brief episodes of transient limb ischemia. According to studies in coronary ischemia, RIPerC during the ischemic event is safe, feasible, and related to a decrease in myocardial injury (7). However, there is limited data about the clinical utility of RIPerC in AIS patients. Only four randomized clinical trials (RCTs) have been completed and published (8–11). All of them demonstrated that RIC is safe and feasible in AIS. One has been conducted to test RIPerC in a prehospital setting in AIS patients and as an adjunct treatment with intravenous alteplase (11). Two other small-size studies were only designed to evaluate the safety and feasibility of RIC in AIS patients recruited within 24 h of onset of symptoms (8) and in alteplase treated patients (9). The last and the largest study included 188 patients with confirmed carotid ischemic stroke within 6 h of symptoms onset (10). None of them demonstrated a significant clinical effect or a significant effect on brain infarction volume growth.

We aim to conduct a multicentre study of pre-hospital RIPerC in AIS patients applied within 8 h of stroke onset. Our hypothesis is that RIPerC would be safe and would induce endogenous neuroprotective phenomena associated with good outcomes in AIS patients treated with revascularization therapies or not.

 

Sevoflurane preconditioning induced endogenous neurogenesis against ischemic brain injury by promoting microglial activation

So when you know ahead of time when your stroke is going to occur you could take this to precondition your brain to produce neurogenesis better. Assuming of course that this is followed up with human clinical tests.
https://www.ncbi.nlm.nih.gov/pubmed/28212538

Li L¹, Saiyin H², Xie J³, Ma L³, Xue L⁴, Wang W⁴, Liang W¹, Yu Q¹.

Author information

Abstract

Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning. This enhancement process is characterized by the promotion of neuroblast proliferation within the subventricular zone (SVZ), migration and differentiation into neurons, and the presence of astrocytes and oligodendrocytes at the site of infarct. The newborn neurons in the sevoflurane preconditioning group showed miniature excitatory postsynaptic currents (mEPSCs), increased synaptophysin and PSD95 staining density, indicating normal neuronal function. Furthermore, long-term behavioral improvement was observed in the sevoflurane preconditioning group consistent with endogenous neurogenesis. Further histological analyses showed that sevoflurane preconditioning accelerated microglial activation, including migration, phagocytosis and secretion of brain-derived neurotrophic factor (BDNF). Intraperitoneal injection of minocycline, a microglial inhibitor, suppressed microglial activation and reversed neurogenesis. Our data showed that sevoflurane preconditioning promoted microglial activities, created a favorable microenvironment for endogenous neurogenesis and accelerated functional reconstruction in the infarct region.

KEYWORDS:

ischemia and reperfusion; microglia; neurogenesis; sevoflurane preconditioning; stem cells

PMID:

28212538

DOI:

10.18632/oncotarget.15325

Comprehensive Insights into the Multi-Antioxidative Mechanisms of Melanin Nanoparticles and Their Application to Protect Brain from Injury in Ischemic Stroke

I can't tell from this if this is preconditioning your brain to withstand the stroke better or applied after your stroke. So ask your doctor which way it is. 

Comprehensive Insights into the Multi-Antioxidative Mechanisms of Melanin Nanoparticles and Their Application to Protect Brain from Injury in Ischemic Stroke

Yanlan Liu, Kelong Ai, Xiaoyuan Ji, Diana Askhatova, Rose Du, Lehui Lu, and Jinjun Shi

J. Am. Chem. Soc., Just Accepted Manuscript

DOI: 10.1021/jacs.6b11013

Publication Date (Web): December 20, 2016

Copyright © 2016 American Chemical Society

Abstract

Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for treating a myriad of important diseases through scavenging excessive reactive oxygen and nitrogen species (RONS), a mechanism critical in disease development and progression. However, similar to antioxidative enzymes, currently studied nano-antioxidants have demonstrated scavenging activity to specific RONS, and sufficient antioxidative effects against multiple RONS generated in diseases remain elusive. Here we propose to develop bioinspired melanin nanoparticles (MeNPs) for more potent and safer antioxidative therapy. While melanin is known to function as a potential radical scavenger, its antioxidative mechanisms are far from clear and its applications for the treatment of RONS-associated diseases have yet to be well explored. In this study, we provide for the first time exhaustive characterization of the activities of MeNPs against multiple RONS including O₂^●−, H₂O₂, ^●NO, ^●OH, and ONOO^–, the main toxic RONS generated in diseases. The potential of MeNPs for antioxidative therapy has also been evaluated in vitro and in a rat model of ischemic stroke. In addition to the broad defense against these RONS, MeNPs can also attenuate the RONS-triggered inflammatory responses through suppressing the expression of inflammatory mediators and cytokines. In vivo results further demonstrate that these unique multi-antioxidative, anti-inflammatory and biocompatible features of MeNPs contribute to their effective protection of ischemic brains with negligible side effects.

Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

Someplace in all these big words is some useful information to be acted upon, which will never occur.  You put an RFP out to researchers, pay for it with foundation grants and write the results up in a stroke protocol available in a public database. 

Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance   

Ján Lehotský^1*, Barbara Tothová¹, Maria Kovalská^1,2, Dušan Dobrota¹, Anna Beňová¹, Dagmar Kalenská¹ and Peter Kaplán¹

• ¹Institute of Medical Biochemistry and BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
• ²Institute of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia

Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic tolerance and recognition of the co-morbid risk factors would result in development of new avenues for exploration of novel therapeutics against ischemia and stroke.

Introduction

Many experimental and clinical studies provide evidence that co-morbid disorders are potential risk factors for development of vascular disorders in humans including stroke (Lehotský et al., 2009a; Kwon et al., 2014). At present, there are several known factors elevating the risk of ischemic stroke which include transient ischemic attack (TIA), arterial diseases, atrial fibrillation, improper diet and/or obesity and physical inactivity (Dirnagl et al., 2009). As it has been verified by many studies, even mild hyperhomocysteinemia (hHcy) may increase the risk for clinical manifestations of stroke, probably due to the pleiotropic biochemical properties of homocysteine (Hcy) and its impact on venous and arterial atherosclerotic modifications (Refsum et al., 1998; Steele et al., 2013; Kwon et al., 2014; Petras et al., 2014; Williams et al., 2014). In fact, Hcy suppresses NO production by endothelial cells and platelets and increases generation of reactive oxygen species (ROS) by the release of arachidonic acid from the platelets. It also inhibits glutathione peroxidase and thus stimulates proliferation of endothelial cells (see Petras et al., 2014, for review). In addition, Hcy has been shown to inhibit methyltransferases, to suppress DNA repair and to facilitate apoptosis when accumulated inside the cells. Autooxidation of Hcy metabolites results in H₂0₂ accumulation (Boldyrev et al., 2013) and challlenging neurons to Hcy metabolites for longer period leads to necrotic cell death (Ziemińska et al., 2003). Clinical studies suggest that elevated homocysteine level frequently parallels progressive aging as well as neurodegenerative and acute disorders of the CNS, e.g., Alzheimer's disease or Parkinson's disease (Dionisio et al., 2010). Designing appropriate animal models relevant to the clinical conditions of human stroke is an important step for studying the disease ethiology. Until now, only sparse studies have been developed to explore the mutual effect of HCy and ischemic preconditioning (IPC) in animal models of ischemic stroke.

In this paper we summarize current overview on homocysteine conversion steps in the organism and present the genetic and metabolic causes of hyperhomocysteinemia-related neurotoxicity. Based on the results from our laboratory, we also document, in this context, that mutual effect of experimental hyperhomocysteinemia (hHCy) and ischemic insult with or without pre-ischemic challenge can have different outcomes on the extent of neuronal degeneration as well as on the intracellular signaling pathways leading to the preconditioning phenomenon.

More at link.

Abstract TP278: Complement Cascade Inhibition Abrogates tPA-mediated Hemorrhage and Brain Edema Following Ischemic Stroke

Tremendous word salad used here which in total I have no understanding. I'd have to say this was written to sound important rather than provide useful information. Unlikely to be of much use in humans since it required administration of C3a receptor antagonist prior to the stroke. 

Abstract TP278: Complement Cascade Inhibition Abrogates tPA-mediated Hemorrhage and Brain Edema Following Ischemic Stroke

1. Xue-Jun Zhao;
2. Timothy M Larkin;
3. Andrew F Ducruet

+ Author Affiliations

1. Univ of Pittsburgh, Pittsburgh, PA

Abstract

Introduction: Tissue plasminogen activator (tPA) remains the only approved pharmacologic treatment for patients with ischemic stroke. Although intravenous thrombolysis improves outcome in a subset of patients, tPA also increases symptomatic hemorrhage and worsens brain edema, thus limiting its clinical applicability. Among several putative mechanisms, plasmin-meditated complement cascade activation likely plays a critical role in the deleterious effects of tPA.

Hypothesis: tPA administration promotes C3 cleavage and complement activation in ischemic brain, and pharmacologic inhibition of the C3a receptor abrogates tPA-mediated hemorrhage and brain edema following reperfused stroke.

Methods: C3a concentrations were assessed using ELISA. Transient focal cerebral ischemia was induced in mice by 60 minutes of middle cerebral artery occlusion (MCAO), with tPA (10mg/kg) or saline injected intravenously at reperfusion. C3a receptor antagonist (1mg/kg) or vehicle was administered 45 minutes prior to MCAO. Infarct volume was determined at 24 hours by TTC staining, neurological function was assessed on a 5-point scale, and brain hemorrhage was quantified using a spectrophotometric assay. Cerebral edema was determined by calculating the difference in volume between ischemic and non-ischemic hemispheres and normalized to infarct volume.

Results: The incubation of tPA with native C3 as well as plasma promotes the generation of C3a. Similarly, intravenous tPA administration dramatically increases cerebral C3a levels in the ischemic hemisphere following MCAO. Intravenous tPA significantly reduces infarct volume (p<0.05) and improves neurological function (p<0.05) in our stroke model. However, tPA also dramatically increases cerebral hemorrhage (p<0.05) and relative cerebral edema (p<0.05). Administration of a C3a receptor antagonist abrogates this hemorrhagic conversion (p<0.05) and brain edema (p<<0 .05="" p="">

Conclusions: Intravenous tPA administration promotes complement activation through C3 cleavage in ischemic brain. Pharmacologic inhibition of the C3a receptor protects against the deleterious side effects of tPA and represents a promising therapeutic strategy for stroke patients

"Beeting" high altitude acclimatization with beet juice

Is our stroke strategy going to be updated to see if beet juice can precondition us to survive a stroke better?  If it can acclimatize us to high altitude then maybe it can mimic the altitudes necessary for preconditioning without having to live there. Or maybe you'd rather go to high altitudes for Training the Brain to Survive Stroke.
This would seem to be so much easier and faster than HBOT but we'll never know since our stroke associations will fail once again in even answering simple questions like this.
When will we have a stroke protocol that has natural foods delivering nitric oxide to us to increase the oxygen carrying capacity of our blood? This sounds extremely fucking important. Do not do this on your own.

"Beeting" high altitude acclimatization with beet juice

Ever since human beings first began climbing the world’s tallest mountains, they have struggled with a basic problem: altitude sickness, caused by lower air pressures which affect the ability of our bodies to take up oxygen.
Or, as actor Jason Clarke says in his role as the climbing guide Rob Hall in the recently released movie, Everest, “Human beings simply aren’t built to function at the cruising altitude of a 747.”
How well humans tolerate high altitudes is highly variable, but the best way to minimize the risk of developing acute mountain sickness (AMS) is acclimatization, or simply spending enough time up high to allow the body to make adjustments to lower oxygen levels.
But what if you could help your body acclimatize more quickly and thoroughly with the help of a natural substance – like beet juice? A team of Norwegian and Swedish researchers decided to see how nitrate-rich beet juice might affect acclimatization on a 39-day expedition to Kathmandu and at 3700 metres in the Rolwaling Valley, Nepal.
Nitric oxide key
One aspect of successful acclimatization is that the blood vessels are able to deliver enough oxygen throughout the body. But normal blood vessel function depends on the body’s ability to naturally produce a compound called nitric oxide (NO).
In healthy people at sea level, production of adequate amounts of NO is not a problem, but with the reduced oxygen availability at high altitude it is a challenge, simply because natural NO production requires oxygen.
But the body has a “back-up system” for NO production at altitude, and it is here that beet juice can help. The secret ingredient in beet juice is high levels of nitrate, which the body can then convert to NO.
Blood vessels work better
Previous research has shown that blood vessels tend to contract at high altitude, so researchers decided to see if they could improve blood vessel function at high altitude simply by having test subjects drink beet juice. They measured blood vessel function with a standard test of arterial endothelial function, a flow-mediated dilatation test (FMD) that uses ultrasound.
In a study recently published in Nitric Oxide: Biology and Chemistry, the researchers showed that consumption of organic nitrate-rich beet juice restored reduced blood vessel function at high altitude.
The researchers behind the study are from the K.G. Jebsen Center for Exercise in Medicine – Cardiac Exercise Research Group (CERG) at the Norwegian University of Science and Technology (NTNU) and the Environmental Physiology Group at Mid-Sweden University in Östersund, Sweden.
First-ever study
The researchers’ project is the first time anyone has studied if consumption of a nitrate-rich juice could have positive effects on blood vessel function at high altitude.
Both men and women were studied with ultrasound to check their blood vessel function, before and during the high altitude expedition. As expected, high altitude made blood vessels contract.
To test if beet juice could make the blood vessels relax again, the test subjects were investigated after drinking two types of beet juice with a 24-hour break between tests.
One of the juices contained high amounts of nitrate while the other type had no nitrate in it (placebo). Neither the study participants nor the researchers knew what type of beet juice each person drank before blood vessel function was measured, and the juices (nitrate-rich versus placebo) were given in a random order.
The study showed that beet juice with high amounts of nitrate made the blood vessels relax and return to normal function, while beet juice with no nitrate (the placebo) did not have any effect.
“Next time you plan a trip at high altitude, maybe it is worth carrying a bottle of beet juice in your backpack,” said the study’s corresponding author, Svein Erik Gaustad, from NTNU’s CERG. “It may be the extra boost your body needs to deliver enough oxygen to your tired muscles and keep you healthy when you are climbing a high mountain.”
http://gemini.no/en/2015/10/beeting-high-altitude-sickness-with-beet-juice/

In-transit Preconditioning Study Shows Neutral Effect in Stroke Patients

But does this new one reject this earlier study? Bad study because they are not measuring the correct items, MRIs can't see penumbra damage, you need PET scans for that. 

Does no one in the stroke world have a functioning brain?
Can using a simple blood-pressure cuff limit damage from strokes caused by decreased blood supply to the brain? On the way to the hospital.

 Does your hospital know? Doctor?
http://www.tctmd.com/show.aspx?id=123068

Key Points:

• Acute stroke patients randomized to treatment with or without remote ischemic preconditioning during EMS transport
• No effect seen on penumbral salvage, final infarct size, progression, as measured by MRI
• Nonetheless, tissue-level analysis hints at some neuroprotection, study authors say

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By L.A. McKeown
Tuesday, November 26, 2013

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Although a prehospital strategy of remote ischemic preconditioning appears safe in patients with acute stroke, magnetic resonance imaging (MRI) results suggest little difference between treated and untreated patients, according to a study published online November 7, 2013, ahead of print in Stroke.
Researchers led by Kristina Dupont Hougaard, MD, of Aarhus University Hospital (Aarhus, Denmark), randomized 443 patients with symptoms of acute stroke (transient ischemic attack, acute ischemic, or hemorrhagic) to IV recombinant tissue plasminogen activator (rtPA) with (n = 247) or without (n = 196) remote ischemic preconditioning between June 2009 and January 2011.
No Clinical Effect Seen
Compared with controls, those randomized to preconditioning had a higher incidence of TIA (17% vs. 8.2%; P = 0.006), and a lower National Institutes of Health (NIH) Stroke Scale score on admission (P = 0.016). However, after reclassification for missing data and other issues, there were no differences in demographic and clinical characteristics between the 2 groups.
At 3 months, there were no differences in penumbral salvage, final infarct size, and infarct growth on MRI between the intervention and control groups (table 1).
Table 1. MRI Results at 3 Months

Median Values	Remote Preconditioning	Controls	P Value
Penumbral Salvage, mL	11.89 (0.53-63.39)	14.10 (1.60-79.82)	0.20
Final Infarct Size, mL	1.63 (0.35-20.09)	1.99 (0.35-16.19)	0.97
Infarct Growth, mL	0 (-0.62 to 8.01)	0.02 (-0.95 to 4.96)	0.79

However, tissue analysis to test for sensitivity to treatment-related effects showed a treatment-dependent change in infarct risk when correcting for the differences in baseline values of mean transit time and perfusion-weighted imaging. Tissue infarct risk by vessel status at arrival and after administration of rtPA showed a reduction of infarct risk in diffusion-weighted imaging-positive tissue at 1 month for patients treated with preconditioning who had no baseline occlusion. In those with persisting occlusion, there also was a reduction of infarct risk except among those with severely prolonged transit times.
Analysis of vessel status at arrival also indicated that in preconditioned patients with no vessel occlusion on admission, there was an overall reduction in the risk of infarction for tissue subjected to preconditioning.
Enough Suggestion of Benefit to Move Ahead
According to the study authors, the patient-level analysis suggests the distribution of diffusion-weighted imaging lesion intensities “seems left shifted for patients treated with [preconditioning] during transportation to the hospital, suggesting a lower degree of cytotoxic edema and therefore potentially less tissue damage when perfusion is promptly restored.” The benefits of the strategy, therefore, “may not be limited to penumbral tissue, but seems to pertain to tissue within the [diffusion-weighted imaging] lesion,” they say.
While any translation of these results into a possible clinical benefit remains unknown, Dr. Hougaard and colleagues say their study is consistent with at least 1 other that has indicated possible neuroprotective effects from remote preconditioning in the poststroke phase in patients with intraarterial stenosis.
The study is limited though by an acknowledged error in randomization. This occurred in the initial period when final consent was not obtained from patients randomized to no preconditioning and as a result those patients were not included in the analysis. “This imbalance may have affected the clinical outcome data but does not affect the tissue-level results in that this approach is inherently adjusted for any imbalance in baseline [perfusion-weighted imaging] and [diffusion-weighted imaging],” they write.
Study Details
Remote preconditioning was performed by ambulance staff during transportation and consisted of 4 inflations of a standard upper limb blood pressure cuff to either 200 or 25 mm Hg above the systolic blood pressure, each lasting 5 minutes and separated by 5 minutes of cuff deflation. Preconditioning also was performed approximately 1 hour before MRI in those patients who participated in the MRI portion of the study. Symptom severity was not assessed prior to preconditioning.

Water Cure for Stroke

Very inflated title, used to pre-treat for 7-10 days prior. So you better schedule your next stroke. And so far only in mice.  Competent? researchers would test to see if this applied in the first hours would save neurons.

Water Cure for Stroke

A simple drink of water laced with hydrogen gas might prevent some of the brain damage resulting from strokes, new research conducted in mice suggests. The gas seems to act as an antioxidant, protecting brain cells from the toxic aftereffects of oxygen starvation that strokes can cause.

Nootropics Reduce the Severity of Brain Trauma

Pre-condition the physiological system to withstand trauma. Fascinating idea but I can't quite see saying, 'I'm going to have a stroke in 3 months, run my brain thru this pre-conditioning'. But maybe we could repurpose some into neuroprotection strategies. 

Nootropics Reduce the Severity of Brain Trauma