Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 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:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. 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 lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Thursday, July 2, 2015

Novel cellular mechanisms for neuroprotection in ischemic preconditioning: a view from inside organelles

So the real question is; After your first stroke should you initiate TIAs in order to precondition the rest of your brain to survive the next stroke?
http://journal.frontiersin.org/article/10.3389/fneur.2015.00115/full?
  • 1Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Science, School of Medicine, Federico II University of Naples, Naples, Italy
  • 2Fondazione IRCSS SDN, Naples, Italy
Ischemic preconditioning represents an important adaptation mechanism of CNS, which results in its increased tolerance to the lethal cerebral ischemia. The molecular mechanisms responsible for the induction and maintenance of ischemic tolerance in the brain are complex and not yet completely clarified. In the last 10 years, great attention has been devoted to unravel the intracellular pathways activated by preconditioning and responsible for the establishing of the tolerant phenotype. Indeed, recent papers have been published supporting the hypothesis that mitochondria might act as master regulators of preconditioning-triggered endogenous neuroprotection due to their ability to control cytosolic calcium homeostasis. More interestingly, the demonstration that functional alterations in the ability of mitochondria and endoplasmic reticulum (ER) managing calcium homeostasis during ischemia, opened a new line of research focused to the role played by mitochondria and ER cross-talk in the pathogenesis of cerebral ischemia in order to identify new molecular mechanisms involved in the ischemic tolerance. In line with these findings and considering that the expression of the three isoforms of the sodium calcium exchanger (NCX), NCX1, NCX2, and NCX3, mainly responsible for the regulation of Ca2+ homeostasis, was reduced during cerebral ischemia, it was investigated whether these proteins might play a role in neuroprotection induced by ischemic tolerance. In this review, evidence supporting the involvement of ER and mitochondria interaction within the preconditioning paradigm will be provided. In particular, the key role played by NCXs in the regulation of Ca2+-homeostasis at the different subcellular compartments will be discussed as new molecular mechanism proposed for the establishing of ischemic tolerant phenotype.

Introduction

Cerebral ischemia is a multifactorial and complex disease (1, 2). Indeed, the intracellular events activated by the loss of perfusion of the brain and responsible for neuronal damage range from impairment of intracellular homeostasis to mitochondrial dysfunction and free radical production (35). The complexity of these events explains the great discrepancy between the frequency of cerebral ischemic accidents and the lack of effective treatments able to inhibit or slow neuronal demise following the ischemic insult. Hence, the urgent need to identify new potential targets for the development of innovative therapeutic strategies able to defend the ischemic brain.
On these premises, in the recent years, the attention of the researchers focused on ischemic tolerance a phenomenon, also known as ischemic preconditioning (IPC), which consists of a sub-lethal anoxic insult that makes the tissue in which it occurs more resistant to a subsequent and potentially lethal ischemia (611). The relevance of this phenomenon is to correlate to the study of the endogenous mechanisms activated in neurons to allow cell survival after a sub-lethal ischemic stimulus. By this way, it is possible to identify new molecular targets useful to develop alternative therapeutic strategies to treat the ischemic disease. The great interest in the cerebral IPC and in the tolerance evoked by itself also comes from the similarity of this phenomenon with those clinical situations occurring in the human brain. Indeed, it is well known that transient ischemic attacks (TIAs) do not cause structural damage but appear to protect brain against a subsequent “stroke” (12, 13).
Therefore, IPC or ischemic tolerance of the brain lie in a natural adaptive process that can be mimicked by a variety of sub-lethal insults, such as transient hypoxia, spreading depression, oxidative stress, hyperthermia, or heat shock, and that increases the tissue tolerance to a subsequent, potentially lethal ischemia. This adaptive cytoprotection is a fundamental property of living cells, which allows them to survive to the exposure to potentially recurrent stressors. This phenomenon was clearly identified in the heart by Murry et al. (14) as preconditioning, or subsequently as ischemic tolerance, and in 1990 it was described also in the brain by Kitagawa et al. (15). Since then, it immediately attracted the interest of clinical and basic neuroscientists for several reasons. First, this biological process became widely recognized as a pertinent and effective experimental instrument to understand how the brain protects itself against ischemia, thereby providing an innovative approach for the discovery of novel neuroprotective strategies. Second, retrospective case-control studies showed a clinical correlate of the phenomenon discovered experimentally.

More at link.

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