Changes in brain polyamine levels following head injury.
The changes in polyamines levels in the brain after closed head injury were studied in rats. At 1 and 15 min, 24 and 48 h after closed head injury cortical tissue from the site of injury, from the contralateral region, and from remote areas were taken. The levels of the diamine putrescine and the polyamines spermine and spermidine were assayed by thin layer liquid chromatography of their dansyl derivatives. Head injury induced a significant increase in putrescine at 48 h at the site of injury and in the frontal lobe of the injured hemisphere, respectively. In the contralateral hemisphere only minor changes in putrescine were found. Spermine and spermidine showed minor changes at that time course. We have previously shown that at 24-48 h after injury, severe edema is found at the site injury. In order to study the role of putrescine in edema formation in this model we treated the traumatized rats with alpha-difluoromethyl-ornithine (DFMO), an inhibitor of ornithine-decarboxylase, the rate limiting enzyme in putrescine biosynthesis. This drug did not affect the level of edema 4 or 48 h after injury although it abolished the increase in putrescine. The effect of DFMO on blood-brain barrier function was studied, using Evans blue extravasation, at the early post-traumatic period (15 min-4 h), where a massive amount of dye is taken up by traumatized brain. No changes in the amount of dye extracted was found after DFMO treatment. On the other hand, DFMO had a beneficial effect on the neurological outcome, as evaluated by a set of clinical criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Shohami
E
E
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Nates
J L
JL
Glantz
L
L
Trembovler
V
V
Shapira
Y
Y
Bachrach
U
U
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000518:Eflornithine / Q000494:pharmacology; D016489:Head Injuries, Closed / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity; D011187:Posture; D011700:Putrescine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013095:Spermidine / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*; D013997:Time Factors
D013096:Spermine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine