Polyamines and NMDA receptors modulate pericapillary astrocyte swelling following cerebral cryo-injury 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. Ornithine decarboxylase activity and polyamine levels were increased over sham controls. The astrocytic swelling, the percentage of the pericapillary space occupied by astrocytic processes, and polyamine levels were reduced to near control levels by the following: (1) alpha-difluoromethylornithine; (2) Ifenprodil; and (3) MK-801. alpha-Difluoromethylornithine is a specific inhibitor of ornithine decarboxylase, Ifenprodil is an inhibitor of the polyamine binding site on the n-methyl-d-aspartate receptor, and MK-801 is an antagonist to n-methyl-d-aspartate binding to the n-methyl-d-aspartate receptor. Addition of putrescine, the product of ornithine decarboxylase activity, reversed the effect of alpha-difluoromethylornithine and restored the pericapillary swelling. Putrescine did not affect the MK-801-induced reduction in pericapillary astrocytic swelling. Therefore, polyamines and the n-methyl-d-aspartate receptor modulate excitotoxic responses to cryo-injury in pericapillary cerebral astrocytes.
Trout
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JJ
Central Electron Microscopy Laboratory, VA Lakeside Medical Center, Chicago, IL, USA.
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Goldstone
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Sahgal
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D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000648:ultrastructure*; D015317:Biogenic Polyamines / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D001930:Brain Injuries / Q000473:pathology*; D002196:Capillaries / Q000166:cytology; D003080:Cold Temperature; D016291:Dizocilpine Maleate / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013223:Statistics as Topic
D015317:Biogenic Polyamines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009955:Ornithine Decarboxylase; C010739:ifenprodil; D000518:Eflornithine