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Inhibiting caspase-9 after injury reduces hypoxic ischemic neuronal injury in the cortex in the newborn rat.

Abstract：

:A broad spectrum caspase inhibitor reduces hypoxic ischemic brain injury. We hypothesized that a specific caspase-9 inhibitor would provide similar protection. Seven-day-old rat pups had the right carotid artery ligated, then were subjected to 2.5 h of 8% oxygen. Caspase-9 activity in the right cortex was measured enzymatically. Caspase-9 activity was increased at 6, 12, and 24 h after injury. LEHD-CHO is a specific cell permeable caspase-9 inhibitor. LEHD-CHO given intracerebroventricularly (i.c.v.) into the brain after the hypoxic period eliminated the increase in caspase-9 activity. The greatest effect was at a dose of 50 microg/pup (1.6 micromol/kg). Fifty-two pups were randomly assigned to receive 50 microg/pup of i.c.v. LEHD-CHO or vehicle immediately after the hypoxic period. The loss of cortical neurons in the right hemisphere 22 days after injury was 52.0+/-8% in the vehicle treated animals, and 25+/-9% in the LEHD-CHO treated animals (P<0.05). Inhibiting caspase-9 activity reduces loss of neurons after brain injury.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Feng Y,Fratkin JD,LeBlanc MH

doi

10.1016/s0304-3940(03)00466-x

keywords:

subject

Has Abstract

pub_date

2003-07-03 00:00:00

pages

201-4

issue

3

eissn

0304-3940

issn

1872-7972

pii

S030439400300466X

journal_volume

344

pub_type

杂志文章

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