POLYAMINES AND NMDA RECEPTORS MODULATE PERICAPILLARY ASTROCYTE SWELLING FOLLOWING CEREBRAL CRYOINJURY IN THE RAT

Four hours following cryo-injury rat cerebral pericapillary astrocytes from the perilesional area were markedly swollen occupying 17% of the pericapillary space as compared to 11% in sham operated controls. Orn ithine decarboxylase activity and polyamine levels were increased over sham controls. The astrocytic swelling the percentage of the pericapi llary space occupied by astrocytic processes, and polyamine levels wer e reduced to near control levels by the following: (1) alpha-difluorom ethylornithine; (2) Ifenprodil; and (3) MK-801. alpha-Difluoromethylor nithine is a specific inhibitor of ornithine decarboxylase, Ifenprodil is an inhibitor of the polyamine binding site on the n-methyl-d-aspar tate receptor, and MK-801 is an antagonist to n-methyl-d-aspartate bin ding to the n-methyl-d-aspartate receptor. Addition of putrescine, the product of ornithine decarboxylase activity, reversed the effect of a -difluoromethylornithine and restored the pericapillary swelling. Putr escine did not affect the MK-801-induced reduction in pericapillary as trocytic swelling. Therefore, polyamines and the n-methyl-d-aspartate receptor modulate excitotoxic responses to cryo-injury in pericapillar y cerebral astrocytes.