Prevention Of Post-Traumatic Epilepsy By Application Of Ceftriaxone Acutely After TBI
Traumatic brain injury (TBI) often leads to epilepsy with a delay that can be weeks to months after the initial trauma. At the biochemical level, the process that leads to epilepsy after TBI is in part mediated by an excess of the excitatory neurotransmitter glutamate whose concentration rises sharply after injury. Ceftriaxone and similar antibiotics, independent of their antibacterial properties, can increase function and expression of the glutamate transport protein, GLT1, which may remove excess glutamate after injury. Accordingly, we propose to test a novel application of ceftriaxone, acutely after brain injury when the biochemical changes leading to post-traumatic epilepsy are first emerging. Specifically we propose to use the established rat lateral fluid percussion injury (LFPI) severe TBI model in a preclinical trial to test whether daily injection of ceftriaxone acutely after TBI can (1) enhance GLT1 function and limit glutamate accumulation after injury, (2) limit cell death and (3) reduce the likelihood of seizures after TBI. As ceftriaxone and similar compounds are already in wide use for antibacterial treatment, we anticipate that positive data from the proposed experiments can be rapidly translated to novel clinical trials.