Heat shock protein HSP70 increases the resistance of cortical cells to glutamate excitotoxicity.
ABSTRACT Preincubation of cultured slices of the olfactory cortex of rat brain with heat shock protein in a concentration of 1 microg/ml protected the pre- and postsynaptic mechanisms of glutamatergic synaptic transmission from glutamate excitotoxicity (50 mM) inducing blockade of excitatory postsynaptic function and reducing presynaptic processes. It was hypothesized that heat shock protein protects AMPA and NMDA receptor-mediated processes.
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Article: Calorie restriction and stroke.[Show abstract] [Hide abstract]
ABSTRACT: ABSTRACT: Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR) or intermittent fasting (IF), extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF); protein chaperones, including heat shock protein 70 (Hsp70) and glucose regulated protein 78 (GRP78); antioxidant enzymes, such as superoxide dismutases (SOD) and heme oxygenase-1 (HO-1), silent information regulator T1 (SIRT1), uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke.Experimental and Translational Stroke Medicine 09/2011; 3:8.
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ABSTRACT: The ability of heat shock proteins (Hsps) to make cells more resistant to most types of metabolic stress has great implications for all post-mitotic cells, especially those of the nervous system. Preventing the loss of neurons is a more parsimonious approach to treatment of injury and disease than is replacement because of the difficulty in reconstructing the complex architecture of the nervous system, the basis for its function storage of information. The discoveries that the 70,kD Hsps are released and that neurons can take them up from the extracellular fluid provides a rationale to investigate how to use them to rescue injured neurons teetering between life and death. We present some of the history behind those discoveries and review the current understanding of the release and uptake of the 70,kD Hsps, discussing the distinct significance these observations have for neurons and some hypotheses about how extracellular Hsps protect neurons from potentially lethal injuries12/2007: pages 257-272;
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ABSTRACT: Blood-borne events play a major role in post bleeding disturbances of the neuronal network. However, very little is known about the early effects of blood plasma, leucocytes, and the red blood cells on the AMPA and NMDA-mediated synaptic responses in the onset of experimental intracranial hemorrhage (ICH). In this study, we used the technique of on-line monitoring of electrophysiological parameters referred to synaptic activity in piriform cortex of SHR rat slice. We exposed the olfactory cortex slices to diluted autologous blood or its components and compared with effects of ferric chloride. Whole blood exerted a total inhibition of synaptic activity in piriform cortex within first 5 min. Dilution of blood induced prolonged epileptic synaptic activation of NMDA receptors. Blood plasma and fraction of leucocytes induced hyperactivation of neurons transforming to epileptiform discharges. Fraction of red blood cells acted biphasic, an initial sharp activity of AMPA- and NMDA-mediated receptors replaced by a following total depression. Our slice-based models of experimental stroke revealed the mechanism of the earliest pathophysiologic events occur in brain tissue during bleeding that may be relevant to the human ICH.General Physiology and Biophysics 09/2013; · 0.88 Impact Factor