期刊
NEUROSCIENCE
卷 142, 期 2, 页码 381-389出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2006.06.053
关键词
neuroprotection; oxygen-glucose deprivation; heat shock protein; hypothermia; inducible nitric oxide synthase; preconditioning
资金
- NIGMS NIH HHS [R01 GM065211] Funding Source: Medline
- NINDS NIH HHS [R01 NS045983] Funding Source: Medline
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 MOS inhibitor, prevented OGD-induced Purkinje cell death/injury. OGD increased the expression of MOS 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 MOS 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. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.
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