Celecoxib treatment improves neurological deficit and reduces selective neuronal loss and glial response in rats following transient middle cerebral artery occlusion.

BACKGROUND: Areas of selective neuronal loss (SNL) represent the first morphological signs of damage in the penumbra region and are considered putative targets for ischemic stroke therapy. Here we performed a novel assessment of measuring the effects of the anti-inflammatory agent, celecoxib, analyzing simultaneously the different neural populations (neurons, astrocytes and microglia cells) in SNL and non-SNL areas.

METHODS: Rats were subjected to 1 hour of middle cerebral artery occlusion (MCAO) and treated with celecoxib 1 h and 24 h after ischemia. Infarct volume measurements and triple immunostaining of neurons (NeuN), microglia (IBA I) and astroglia (GFAP) were performed after 12 h and 48 h of reperfusion. Motor response was tested by standard behavioural assays at 3 h, 12 h, 24 h and 48 h.

RESULTS: Confocal analysis revealed that the percentage of SNL areas, microglia densities and glial activation increased at 48 h of reperfusion. Celecoxib treatment improved the neurological deficit, reduced the infarct volume by 50% after 48 h of reperfusion, and resulted in a reduced percentage of SNL areas and microglia and astroglia reactivity after 48 h of reperfusion.

CONCLUSIONS: This study proves for the first time that celecoxib presents post-ischemic neuroprotective effects in a transient MCAO model, prevents, or delays, the presence of SNL areas and reduces glial activation.