Taming Glutamate Excitotoxicity: Strategic Pathway Modulation for Neuroprotection

But is glutamate poisoning really the problem?
This research from 2003 suggests that maybe glutamate poisoning is not really the factor 


Or is taurine better? Does anyone ever think about stroke problems at all?

Mechanisms Underlying Taurine Protection Against Glutamate-Induced Neurotoxicity

Or maybe lithium?

Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity.

 

 

Taming Glutamate Excitotoxicity: Strategic Pathway Modulation for Neuroprotection 

• Ming Jia,
• Steve A. Noutong Njapo,
• Vaibhav Rastogi,
• Vishnumurthy Shushrutha Hedna

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Abstract

Much work has been carried out in recent years showing that elevated glutamate levels in the extracellular environment of the central nervous system play a pivotal role in neurodegeneration in acute CNS injuries. With the elucidation of the mechanism governing glutamate excitotoxicity, researchers are devising therapeutic strategies to target different parts of the pathway which begins with glutamate accumulation and ultimately results in neuronal cell death. In this article, we review some of the major classes of agents that are currently being investigated and highlight some of the key studies for each. Glutamate scavenging is a relatively new approach that directly decreases glutamate levels in the brain, thus preventing excitotoxicity. Nitric oxide inhibitors and free radical scavengers are more well-studied strategies that continue to yield promising results.

M. Jia and S. A. Noutong Njapa are co-first authors of this work.

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Mechanisms Underlying Taurine Protection Against Glutamate-Induced Neurotoxicity

And since glutamate poisoning is one of the components of the neuronal cascade of death your doctor and researcher need to be following this. Ask whether they are considering testosterone reduction to help in reducing glutamate problems. And is your great stroke association putting all this together into their strategy to reduce stroke disability?  Of course not, we don't have one yet.
http://cjns.metapress.com/content/q57v7qu0337w6q14/?id=Q57V7QU0337W6Q14

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Authors

Hai-Bo Ye¹, Hai-Bo Shi¹, Shan-Kai Yin¹

¹Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, China

Abstract

Taurine appears to exert potent protections against glutamate (Glu)-induced injury to neurons, but the underlying molecular mechanisms are not fully understood. The possibly protected targets consist of the plasma membrane and the mitochondrial as well as endoplasmic reticulum (ER) membranes. Protection may be provided through a variety of effects, including the prevention of membrane depolarization, neuronal excitotoxicity and mitochondrial energy failure, increases in intracellular free calcium ([Ca²⁺]i), activation of calpain, and reduction of Bcl-2 levels. These activities are likely to be linked spatially and temporally in the neuroprotective functions of taurine. In addition, events that occur downstream of Glu stimulation, including altered enzymatic activities, apoptotic pathways, and necrosis triggered by the increased [Ca²⁺]i, can be inhibited by taurine. This review discusses the possible molecular mechanisms of taurine against Glu-induced neuronal injury, providing a better understanding of the protective processes, which might be helpful in the development of novel interventional strategies.

Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells

Someone should be able to translate taurine into some kind of therapy protocol, or at least tell us how to get it to the brain. I'm really depressed that for all the research out there no one is even trying to translate it into a therapy protocol. I can't do everything.
http://www.sciencedirect.com/science/article/pii/S1873506112000232

Abstract

This study reports an effect of taurine (1–10 mM) increasing markedly (120%) the number of neural precursor cells (NPCs) from adult mouse subventricular zone, cultured as neurospheres. This effect is one of the highest reported for adult neural precursor cells. Taurine-containing cultures showed 73-120% more cells than controls, after 24 and 96 h in culture, respectively. Taurine effect is due to enhanced proliferation as assessed by BrdU incorporation assays. In taurine cultures BrdU incorporation was markedly higher than controls from 1.5 to 48 h, with the maximal difference found at 1.5 h. This effect of taurine reproduced at every passage with the same window time. Taurine effects are not mimicked by glycine, alanine or GABA. Clonal efficiency values of 3.6% for taurine cultures and 1.3% for control cultures suggest a taurine influence on both, progenitor and stem cells. Upon differentiation, the proportion of neurons in control and taurine cultures was 3.1% (± 0.5) and 10.2% (± 0.8), respectively. These results are relevant for taurine implication in brain development as well as in adult neurogenesis. Possible mechanisms underlying taurine effects on cell proliferation are discussed.

Here is a full paper on taurine:

Physiological Actions of Taurine 63 pages

http://physrev.physiology.org/content/72/1/101.full.pdf

Synchrotron Techniques and Research: Objectives at the K-Edge (Novel Investigations of the Role of Sulfur in Stroke Pathogenesis using Synchrotron Bas

I didn't understand this one but someone will. From the 2011 Canadian Stroke Congress.
page 66 here:
http://www.strokecongress.org/2011/wp-content/uploads/2011/12/CSC_Abstracts.pdf
Our goal is to use synchrotron radiation and sophisticated spectroscopic techniques to generate spatial maps of sulfur distribution and its chemical forms in rodent models of stroke, to guide the development of biomarkers of stroke pathology, provide insight into current neuroprotective treatments, and aid in designing novel treatment strategies. Thiols, disulfides, and sulfoxides have been strongly implicated with peroxidative damage following stroke, and taurine may play a pertinent role as a neurotransmitter/modulator for several key neuronal pathways.
We will reveal our initial results of an explorative study of the capabilities of X-ray absorption spectroscopy (XAS), at the sulfur K-edge, to investigate the role of sulfur containing molecules in the brain following ischemic insult.
Initial experiments were conducted at the Stanford synchrotron radiation lightsource (SSRL), using XAS at thesulfur K-edge (2460-2490 eV). Air-dried, formalin-fixed, freeze-dried, and frozen tissue sections (10-μm-thick) were analysed to determine the most suitable sample preparation method. Characteristic spectral signatures
were determined for micro-dissected brain regions (brain stem, cerebellum, hippocampus), and the sulfur speciation compared between control (sham operated) and diseased animals at 12 hours or 7 days post global cerebral ischemia (rat 2-vessel occlusion model). The results reveal for the first time, in-situ, the thiol, disulfide,
sulfoxide, taurine, and sulfate composition of healthy and postischemic brain tissue. Our results parallel those obtained with conventional assays, with the advantage that our method will shortly be applied with an imaging capability to determine spatial distribution across brain regions of varying susceptibility to ischemia (Canadian
Light Source). Future studies will image the distribution of the sulfur species, at sub-cellular resolution (< 1 μm), in the same tissue sample. Specifically, this method will allow thiol/disulfide ratios, sulfoxide accumulation, and the role of taurine as a neurotransmitter/modulator in ischemic brain injury and neuroplasticity to be studied as never before.