The effect of age on cerebral oedema, cerebral infarction and neuroprotective potential in experimental occlusive stroke.

Abstract

A model of occlusive stroke in the aging brain has been developed and used to evaluate the effects of age upon cerebral infarction, cerebral oedema and neuroprotective potential. Focal ischaemia following left middle cerebral artery occlusion has been compared in aged (30 month) and adult (< 17 month) rats, with histological assessment of infarct volume and analysis of specific gravity as an index of cerebral oedema. Aging was associated with a significant increase in cerebral infarct size. The mean infarct volume in aged rats was 40.5% +/- 2.6% of the hemisphere volume, compared to 30.9% +/- 0.7% in adults (p < 0.01). Pre-treatment with the competitive N-Methyl-D-Aspartate (NMDA) receptor antagonist 3-(2-Carboxy Piperazin-4-yl)Propyl-l-Phosphonate (D-CPP-ene) reduced infarct volumes in both age groups to 33.0% +/- 1.8% and 20.7% +/- 3.2% in aged and adult animals, respectively (p < 0.05). There was significantly less oedema of the cerebral cortex in D-CPP-ene pre-treated rats; mean cortical specific gravity 4 hours post-infarction was 1.0381 +/- 0.0013 in untreated aged rats and 1.0391 +/- 0.0014 in untreated adults, compared to 1.0458 +/- 0.0031 in treated aged rats and 1.0442 +/- 0.0014 in treated adults (p < 0.05). At 24 hours post-infarction, D-CPP-ene pre-treated aged rats had a mean cortical specific gravity of 1.0403 +/- 0.0006 compared to 1.0361 +/- 0.0014 in untreated aged animals (p < 0.05). This study has demonstrated an age-related increase in cerebral infarct size, but has shown that the aging brain is amenable to neuroprotection by NMDA receptor antagonism.