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

TL;DR

This study demonstrates that nimesulide, a cyclooxygenase-2 inhibitor, provides significant and lasting neuroprotection to hippocampal neurons after transient global cerebral ischemia in gerbils, even when administered up to 24 hours post-ischemia.

Contribution

It is the first to show that nimesulide confers long-lasting neuroprotection when given after ischemia, highlighting its potential for therapeutic use in stroke.

Findings

Nimesulide significantly reduces hippocampal neuronal damage.

Protection is effective even when treatment is delayed 24 hours post-ischemia.

Neuroprotective effects are maintained for at least 30 days.

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.