Impairment of the ability of the injured aged brain in elevating urate and ascorbate.
Urate and ascorbate play a major role in the defense mechanism of the brain against oxidative damage induced by traumatic brain injury. The severity and extent of brain damage are known to increase with age. This may be due to different basal levels of endogenous antioxidants, and/or to impaired ability of the old brain to recruit and elevate the levels of antioxidants following injury. To investigate this hypothesis, we measured basal ascorbate and urate levels in the hippocampus, using microdialysis in young, adults and old rats, and performed closed head injury (CHI) in young (5-6 weeks) and old rats (19-20 months). Basal ascorbate, but not urate levels in old rats were significantly lower than in the adults. The ability of the old rats to increase ascorbate levels after CHI was significantly lower than that of the young ones, as indicated by lower levels of ascorbate and urate in the dialysate of old rats. This lower level of antioxidant mobilization in the old brain may explain the extended damage found in histology. Evaluation of hippocampal cell loss (p<0.05) and axonal degeneration in the corpus callosum showed more extensive damage in old as compared to young rats (chi(2)=4.25; p<0.05). These findings shed more light on the susceptibility of old rat brain to CHI-induced oxidative damage.
Moor
Eitan
E
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120 Israel.
Shohami
Esther
E
Kanevsky
Ester
E
Grigoriadis
Nikolaos
N
Symeonidou
Constantina
C
Kohen
Ron
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000032:analysis*; D001205:Ascorbic Acid / Q000032:analysis*; D001369:Axons / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism*; D003337:Corpus Callosum / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000032:analysis*
D000975:Antioxidants; D014527:Uric Acid; D001205:Ascorbic Acid