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|Title:||Hsp70 Involvement in Hyperthermic Preconditioning of Excitotoxic Neuronal Damage in the Hippocampus||Authors:||Muna Khalid Alrumh||Supervisor:||Dr. Alfred Pavlik||Keywords:||Hsp70 Neuronal Damage Hippocampus||Issue Date:||2013||Publisher:||Kuwait university - college of graduate studies||Abstract:||iv Abstract Heat shock protein Hsp70 is recognized as a major stress protein affording significant protection against many cellular stress types like hyperthermia, ischemia and trauma. In the brain, hyperthermia induced Hsp70 protein in oligodendrocytes and microglia but not in astrocytes and most forebrain neurons, which contained considerable amount of constitutive Hsc70. Preconditioning nervous tissue with Hsp70, which had been induced in neurons, effectively protected against above mentioned stresses. In this study, we used a model of excitotoxic damage in hippocampal CA3 to elucidate possibility if whole body hyperthermia (WBH) would precondition the excitotoxic damage and biochemical disturbance despite the absence of Hsp70 induction in hippocampal neurons following WBH. Young female rats were subjected to preconditioning heat stress (HS: 41.50 x 30 min) and after 4, 24 or 72 hours they were anesthetized (urethane, 1.5g/kg) and injected with intracerebroventricular (icv) kainate (KA: 0.05, 0.15 or 0.6 μg). Rats were sacrificed 4 hours after KA injection. Vibratome sections were processed for Nissl staining, and Hsp70, Hsc70, c-Fos, microglial and astrocyte immunohistochemistry (IHC). IHC stained sections were evaluated quantitatively by image analysis and non-parametric statistics. KA-induced damage was dose dependent and extended through CA3 to CA4 and the hillus of the hippocampus with the highest (0.6 μg) KA dose. The HS preconditioning decreased the hippocampal CA3a damage and c-Fos expression attenuation only after the lowest (0.05 μg) KA dosage by about 60 % in 4 and 72 hour intervals investigated. Blocking of Hsp70 expression by quercetine injection pre- and post-HS significantly abolished the HS-induced protection at 4 hours but it did not so at 72 hours after HS. To further elucidate the role of Hsp70, we injected the heat-stress preconditioned animals icv with 50 μg PES/pifithrine, a new low molecular inhibitor of Hsp70 but this treatment did not attenuated heat induced-tolerance to kainate. Then, injecting the same icv dose of PES/pifithrine to rats treated only with kainate disclosed that PES/pifithrine alone was protecting CA3a neurons against KA-induced excitotoxic damage. These results suggest that either Hsp70 produced in glial/vascular cells might be responsible for the observed early protection against excitotoxicity or the early observed protection would be caused by other type of Hsps in any type of CA3a cells, including pyramidal neurons.||URI:||http://hdl.handle.net/123456789/257|
|Appears in Programs:||0530 Physiology (M.Sc.)|
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