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.