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Administration of N‐acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke
Author(s) -
Khan Mushfiquddin,
Sekhon Bipanjeet,
Jatana Manu,
Giri Shailendra,
Gilg Anne G.,
Sekhon Charanpal,
Singh Inderjit,
Singh Avtar K.
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20087
Subject(s) - medicine , neuroprotection , ischemia , pharmacology , proinflammatory cytokine , stroke (engine) , acetylcysteine , reperfusion injury , nitric oxide synthase , inflammation , microglia , anesthesia , cerebral infarction , infarction , middle cerebral artery , brain ischemia , nitric oxide , immunology , chemistry , antioxidant , biochemistry , myocardial infarction , mechanical engineering , engineering
Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N‐acetylcysteine (NAC) has been found to attenuate the cerebral ischemia‐reperfusion injury in a rat model of experimental stroke. This study was undertaken to investigate the neuroprotective potential of NAC administered after ischemic events in experimental stroke. FCI was induced for 30 min by occluding the middle cerebral artery (MCA). NAC (150 mg/kg) was administered intraperitoneally at the time of reperfusion followed by another dose 6 hr later. Animals were sacrificed after 24 hr of reperfusion. The cerebral infarct consistently involved the cortex and striatum. Infarction was assessed by staining the brain sections with 2,3,5‐triphenyltetrazolium chloride. Animals treated with NAC showed a significant reduction in infarct area and infarct volume and an improvement in neurologic scores and glutathione level. Reduction in infarction was significant even when a single dose of NAC was administered at 6 hr of reperfusion. Immunohistochemical and quantitative real‐time PCR studies demonstrated a reduction in the expression of proinflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin 1β (IL‐1β) and inducible nitric oxide synthase (iNOS) in NAC compared to that in vehicle‐treated animals. The expression of activated macrophage/microglia (ED1) and apoptotic cell death in ischemic brain was also reduced by NAC treatment. These results indicate that in a rat model of experimental stroke, administration of NAC even after ischemia onset protected the brain from free radical injury, apoptosis, and inflammation, with a wide treatment window. © 2004 Wiley‐Liss, Inc.