Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 493 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:

Friday, February 3, 2017

Prolonged Activation of Invariant Natural Killer T Cells and TH2-Skewed Immunity in Stroke Patients

I got nothing out of this. Our great stroke association should explain each stroke research article and tell us how it improves stroke recovery. But since we have fucking failures of stroke associations YOU will have to do all this work yourself. All 10 million survivors each year analyzing research to see how it could help them.
imageConnie H. Y. Wong1,2*, imageCraig N. Jenne2,3, imagePatrick P. Tam3, imageCaroline Léger3, imageAndres Venegas4, imageKarla Ryckborst4, imageMichael D. Hill4 and imagePaul Kubes2,3*
  • 1Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Science, Monash University, Melbourne, VIC, Australia
  • 2Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
  • 3Department of Critical Care, Snyder Institute for Critical Care, University of Calgary, Calgary, AB, Canada
  • 4Stroke Unit, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
Background: Infection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (TH2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (iNKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of iNKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections.
Methods and results: We obtained blood from stroke patients and matching controls to perform flow cytometry and multiplex measurement of inflammatory mediators. Our data suggest a pronounced activation of iNKT cells in stroke patients as compared with matched Healthy and Hospital control patients. The magnitude of iNKT activation is positively correlated with the severity of stroke, supporting the hypothesis that iNKT cells may contribute in the modulation of the host immune response after stroke-associated brain injury. In addition, stroke severity is closely correlated with decreased TH1/TH2 ratio, increased production of interleukin (IL)-10, with infected stroke patients showing exacerbated production of IL-10.
Conclusion: Stroke triggers a robust and sustained shift in systemic immunity in patients, including specific lymphopenia, robust activation of iNKT cells, systemic production of IL-10, and a prolonged TH2-skewed immunity, all are potential contributors to severe immune suppression seen in patients after stroke. Future studies with large sample size will provide potential causality relationship insights.


Ischemic stroke is a common and debilitating cerebrovascular event that is caused by the sudden impairment of blood flow to regions of the brain. Up to 65% of stroke patients develop infection (1), and more than 30% die as a direct result (2), making infection a highly relevant clinical problem. Increased bacterial infections in stroke patients suggest that the immune response, which normally is responsible for eliminating these infections in healthy individuals, is impaired after ischemic brain injury. Emerging evidence now indicates that stroke induces profound systemic immune effects (3), including severe reductions in the number of circulating lymphocytes and altered lymphocyte and monocyte function (4, 5). Despite accumulating evidence supporting the notion of a stroke-induced peripheral anti-inflammatory state in response to the overwhelming cerebral inflammation following stroke (6), the molecular mechanisms resulting in systemic immune suppression after stroke in humans have, for the most part, remained elusive.
The balance between pro- and anti-inflammatory cytokines determines the proficiency of the immunological response and has the potential to influence both the fate of the injured brain and the threshold to developing complications such as infection. In the clinical setting of stroke, the balance between pro- and anti-inflammatory cytokines is an important prognostic factor (6). Stroke patients were found to present with a rapid increase in plasma cytokines resulting in a low ratio of pro-inflammatory tumor necrosis factor alpha (TNFα) to anti-inflammatory interleukin (IL)-10, preceding the appearance of infection (7). This observation supports the hypothesis of stroke-induced immunosuppression via a decrease in systemic TH1/TH2 ratio. Surprisingly, poststroke T cell priming to an increased IL-4 expression following mitogenic stimulation was evident in the peripheral blood of patients in the post-acute phase of stroke (8). Despite this, it is important to note of the timing of this apparent immune shift following stroke. Generally, lymphocytes and the adaptive immune response could be expected to control infection 5–7 days after stroke, dysfunction in these cells does not explain the observed increase in infection in the first 3 days (9). In addition, the development of infection in the mouse model of stroke takes only a few hours (10). This difference in the temporal development of a TH2-skewed immune response following stroke suggests the shift must be orchestrated by mechanisms distinct from the conventional adaptive immune response.
In our previous work with an experimental model of ischemic stroke, we demonstrated that invariant natural killer T (iNKT) cells play an important role in regulating poststroke immunosuppression and infections (10). iNKT cells are a distinct lymphocyte lineage that can rapidly produce large quantities of both TH1 [interferon gamma (IFNγ), TNFα] and TH2 (IL-4, IL-10) cytokines, giving these cells a unique ability to have wide-ranging roles in the regulation of immunity (11). Despite their location in a site remote from the brain, we showed that circulating iNKT cells and iNKT cells resident in the liver were able to rapidly respond to ischemic stroke, and release predominantly a TH2-type cytokine IL-10, rendering the host more susceptible to bacterial infections (10). This intriguing finding highlighted a connection between brain injury sustained following ischemic stroke and robust functional impairment of peripheral immune cells, in particularly, iNKT cells. In this prospective clinical study, we aimed to delineate the systemic immune profile of stroke patients over time. Specifically, we conducted a matched cohort study to characterize the temporal TH1/TH2 cytokine, chemokine, and iNKT cell response in the blood of stroke patients up to 3 months after stroke onset. In addition, we sought to explore whether an association exists between stroke severity with the degree of peripheral iNKT cell activation and TH2-skewed systemic immunity.

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