Cyclosporin ameliorates traumatic brain-injury-induced alterations of hippocampal synaptic plasticity.
Although traumatic brain injury (TBI) often results in impaired learning and memory functions, the underlying mechanisms are unknown and there are currently no treatments that can preserve such functions. We studied plasticity at CA3-CA1 synapses in hippocampal slices from rats subjected to controlled cortical impact TBI. Long-term potentiation (LTP) of synaptic transmission was markedly impaired, whereas long-term depression (LTD) was enhanced, 48 h following TBI when compared to unoperated and sham control rats. Post-TBI administration of cyclosporin A, a compound that stabilizes mitochondrial function, resulted in a highly significant amelioration of the impairment of LTP and completely prevented the enhancement of LTD. Our data suggest that alterations in hippocampal synaptic plasticity may be responsible for learning and memory deficits resulting from TBI and that agents such as cyclosporin A that stabilize mitochondrial function may be effective treatments for TBI.
Albensi
B C
BC
Sanders-Brown Research Center on Aging and Department of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA.
Sullivan
P G
PG
Thompson
M B
MB
Scheff
S W
SW
Mattson
M P
MP
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D003288:Contusions / Q000503:physiopathology*; D016572:Cyclosporine / Q000494:pharmacology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D004791:Enzyme Inhibitors; D016572:Cyclosporine