Accumulation of exogenous polyamines in gerbil brain after ischemia.
Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [14C]spermine was transiently increased after ischemia, peaking at 150% of control by 12-13 h and subsiding by 24 h. Intravenous injections of [3H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that: 1. Active cellular uptake of spermine is transiently increased early after ischemia; 2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and 3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia.
Gilad
G M
GM
Neuropsychiatry Branch, NIMH Neuroscience Research Center at Saint Elizabeths, Washington, DC 20032.
Gilad
V H
VH
Wyatt
R J
RJ
D000818:Animals; D001345:Autoradiography; D015317:Biogenic Polyamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D015317:Biogenic Polyamines; D013096:Spermine; D013095:Spermidine; D011700:Putrescine