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Novel mediators of ischemic preconditioning induced neuroprotection
Author(s) -
Dhodda V. K.,
Sailor K.,
Dempsey R. J.,
Vemuganti R. L. R.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.42_3.x
Subject(s) - neuroprotection , smad , ischemic preconditioning , medicine , ischemia , p38 mitogen activated protein kinases , neuroscience , pharmacology , mapk/erk pathway , microbiology and biotechnology , signal transduction , biology
A brief ischemic episode induces protection against a subsequent severe ischemic insult. This phenomenon, known as ischemic preconditioning (PC) might be mediated by the activation of several genes of the second messenger signalling pathways. A 60‐min transient middle cerebral artery occlusion (MCAO) in adult, SHR rats results in an infarct encompassing cerebral cortex and striatum by 24 h reperfusion. Present study observed that a 10‐min PC, 3 days before the 60 min transient MCAO, results in a 30% reduction in the infarct volume. To understand the molecular mechanisms of the PC induced neuroprotection, we analyzed the mRNA expression profiles of rat cerebral cortex at 6, 24 and 72 h after a 10‐min transient MCAO by using Affymetrix GeneChip and real‐time PCR. Expression of the members of TGF‐β signalling (TGF‐β1, p 38 MAP kinase, Smad 1 and Smad 7) is observed to be up‐regulated after PC. This pathway plays an essential role in tissue repair and immune homeostasis, but not hitherto implicated in PC induced neuroprotection. TGF‐β1 enhances Smad transcriptional activity through activation of P38 gene expression to induce neuroprotection. Consistent with previous studies, expression of several neuroprotective genes including HSP70, HSP27, HO‐1, MT‐1/MT‐2 and IL‐6, were also observed to be up‐regulated after PC. These studies shows that TGF‐β1/p38 MAP‐kinase signalling pathway is a promising target for developing drugs to limit ischemic neuronal damage. Acknowledgements: Funded by AHA.