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Hypothermic preconditioning reduces Purkinje cell death possibly by preventing the over-expression of inducible nitric oxide synthase in rat cerebellar slices after an in vitro simulated ischemia.

Abstract：

:We showed that hypothermic preconditioning (HPC) increased survival of Purkinje neurons in rat cerebellar slices after oxygen-glucose deprivation (OGD). HPC also reduced the OGD-increased expression of high mobility group I (Y) proteins, a transcription factor that can enhance inducible nitric oxide synthase (iNOS) expression. iNOS is a putatively damaging protein that contributes to ischemic brain injury. Heat shock proteins (HSPs) can be induced by various stimuli to protect cells. We hypothesize that HPC induces neuroprotection by reducing the expression of putatively damaging proteins such as iNOS and/or by increasing the expression of putatively protective proteins such as HSPs. Cerebellar slices were prepared from adult male Sprague-Dawley rats and incubated in circulating artificial cerebrospinal fluid. OGD was for 20 min at 37 degrees C and was followed by a 5-h recovery at 37 degrees C before slices were used for morphological, immunohistochemical and Western analyses. HPC was performed by incubating slices at 33 degrees C for 20 min at 1 h before the OGD. HPC and aminoguanidine, an iNOS inhibitor, prevented OGD-induced Purkinje cell death/injury. OGD increased the expression of iNOS and nitrosylated proteins. These increases were abolished by aminoguanidine and HPC. Interestingly, the expression of HSP70 was increased by OGD but not by HPC. Our results suggest that an increased iNOS expression contributes to the pathophysiology of OGD-induced Purkinje neuronal death in our model. Our results also suggest the involvement of inhibiting the expression of the putatively damaging iNOS proteins in the HPC-induced neuroprotection. HSP70 may not contribute to the HPC-induced neuroprotection.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Yuan HB,Huang Y,Zheng S,Zuo Z

doi

10.1016/j.neuroscience.2006.06.053

subject

Has Abstract

pub_date

2006-10-13 00:00:00

pages

381-9

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(06)00884-0

journal_volume

142

pub_type

杂志文章

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Hypothermic preconditioning reduces Purkinje cell death possibly by preventing the over-expression of inducible nitric oxide synthase in rat cerebellar slices after an in vitro simulated ischemia.