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Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia

Candelario-Jalil, Eduardo and Alvarez, Dalia and Gonzalez-Falcon, Armando and Garcia-Cabrera, Michel and Martinez-Sanchez, Gregorio and Merino, Nelson and Giuliani, Attilia and Leon, Olga S. (2002) Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia. [Journal (Paginated)]

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Abstract

Cyclooxygenase-2 is involved in the inflammatory component of the ischemic cascade, playing an important role in the delayed progression of the brain damage. The present study evaluated the pharmacological effects of the selective cyclooxygenase-2 inhibitor nimesulide on delayed neuronal death of hippocampal CA1 neurons following transient global cerebral ischemia in gerbils. Administration of therapeutically relevant doses of nimesulide (3, 6 and 12 mg/kg; i.p.) 30 min before ischemia and at 6, 12, 24, 48 and 72 h after ischemia significantly (P<0.01) reduced hippocampal neuronal damage. Treatment with a single dose of nimesulide given 30 min before ischemia also resulted in a significant increase in the number of healthy neurons in the hippocampal CA1 sector 7 days after ischemia. Of interest is the finding that nimesulide rescued CA1 pyramidal neurons from ischemic death even when treatment was delayed until 24 h after ischemia (34+/-9% protection). Neuroprotective effect of nimesulide is still evident 30 days after the ischemic episode, providing the first experimental evidence that cyclooxygenase-2 inhibitors confer a long-lasting neuroprotection. Oral administration of nimesulide was also able to significantly reduce brain damage, suggesting that protective effects are independent of the route of administration. The present study confirms the ability of cyclooxygenase-2 inhibitors to reduce brain damage induced by cerebral ischemia and indicates that nimesulide can provide protection when administered for up to 24 h post-ischemia.

Item Type:Journal (Paginated)
Keywords:nimesulide; cerebral ischemia; delayed neuronal death; hippocampal CA1 sector; neuroprotection; gerbils; neurodegeneration; prostaglandin E2; stroke
Subjects:Neuroscience > Neurochemistry
ID Code:5643
Deposited By:Candelario-Jalil, Dr Eduardo
Deposited On:20 Aug 2007
Last Modified:11 Mar 2011 08:56

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