Differential response of neural cells to trauma-induced free radical production in vitro.
CNS trauma has been associated with an increase in free radical production, but the cellular sources of this increase or the mechanism involved in the production of free radicals are not known. We, therefore, investigated the effects of trauma on free radical production in cultured neurons, astrocytes and BV-2 microglial cells. Free radicals were measured with the fluorescent dye DCFDA following in vitro trauma. At 30 and 60 min following trauma, there was a 132% and 64% increase, respectively, in free radical production in neurons when compared to controls. In astrocytes, there was a 94% and 133% increase at 30 and 60 min, respectively. Microglial cells, however, displayed no significant increase in free radicals at 30, 60 or 120 min following trauma. Since trauma can induce the mitochondrial permeability transition (MPT), a process associated with mitochondrial dysfunction, we further investigated whether cyclosporin A (CsA), an agent known to block the MPT, could prevent free radical formation following trauma. In neurons CsA did not block free radical production at 30 min but blocked it by 90% at 60 min. In contrast, in astrocytes CsA completely blocked free radical production at 30 min but did not block it at 60 min. Our results indicate that a differential sensitivity to trauma-induced free radical production exists in neural cells; that the MPT may be involved in the production of free radical post-trauma; and that the CsA-sensitive phase of free radical production is different in neurons and astrocytes.
Panickar
K S
KS
Department of Pathology, University of Miami School of Medicine, Florida 33101, USA.
Jayakumar
A R
AR
Norenberg
M D
MD
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012016:Reference Values; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors
D065095:Calcineurin Inhibitors; D005609:Free Radicals; D016572:Cyclosporine; D016559:Tacrolimus