TY - JOUR
T1 - Changes in brain polyamine levels following head injury
AU - Shohami, E.
AU - Nates, J. L.
AU - Glantz, L.
AU - Trembovler, V.
AU - Shapira, Y.
AU - Bachrach, U.
PY - 1992/8
Y1 - 1992/8
N2 - 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 α-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. These results demonstrate the activation of the biosynthetic pathway of polyamines as a result of primary mechanical injury to the brain. Their role in early BBB disruption and in the development of edema at the delayed (48 h) phase can be ruled out based on the present results, since DFMO, despite its effective inhibition of putrescine, was ineffective in protecting BBB or reducing edema. However, the improvement of the clinical outcome points to a role these compounds might play in the development of delayed neuronal damage.
AB - 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 α-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. These results demonstrate the activation of the biosynthetic pathway of polyamines as a result of primary mechanical injury to the brain. Their role in early BBB disruption and in the development of edema at the delayed (48 h) phase can be ruled out based on the present results, since DFMO, despite its effective inhibition of putrescine, was ineffective in protecting BBB or reducing edema. However, the improvement of the clinical outcome points to a role these compounds might play in the development of delayed neuronal damage.
UR - http://www.scopus.com/inward/record.url?scp=0026683215&partnerID=8YFLogxK
U2 - 10.1016/0014-4886(92)90126-B
DO - 10.1016/0014-4886(92)90126-B
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 1499692
AN - SCOPUS:0026683215
SN - 0014-4886
VL - 117
SP - 189
EP - 195
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -