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Heat shock response in the central nervous system

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Abstract

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemis stress confers protection from a subsequent ischemic insult.

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  1. Neurology and Medical Service, Massachusetts General Hospital, Harvard Medical School, Kennedy 915, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA

    W. J. Koroshetz

  2. Medical Service, Massachusetts General Hospital, Harvard Medical School, Suite 4002, Massachusetts General Hospital East, 02129, Charlestown, Massachusetts, USA

    J. V. Bonventre

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Koroshetz, W.J., Bonventre, J.V. Heat shock response in the central nervous system. Experientia 50, 1085–1091 (1994). https://doi.org/10.1007/BF01923465

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