Development and Post Insult Plasticity

Abstract

Abstract *Don Shin, *Elisa Zanier, *David Hovda, and *Raman Sankar ( *David Geffen School of Medicine at UCLA Departments of Pediatrics and Neurology, Los Angeles, CA, U.S.A. ). Purpose: Early posttraumatic seizures (EPTS) are more common in the pediatric population and sequelae of traumatic brain injury (TBI) in humans include epilepsy. Animal and human data demonstrate significant alterations in regional cerebral metabolic rate for glucose during the acute period following TBI. In immature rat pups of postnatal age 17 days (P17), moderate fluid percussion injury (FPI) alone does not result in discernible cellular injury. However, seizures impose significant demands on energy metabolism, and energy failure can contribute to cellular injury in vulnerable regions of the brain, such as the hippocampus. We hypothesized that TBI may confer added vulnerability to seizure-induced brain damage in the aftermath of TBI. Methods: P17 rats were pretreated with LiCl and then subjected the following day to moderate lateral FPI using loss of consciousness and responsivity to toe pinch as criteria for injury severity. One hour after FPI or sham treatment, rats were given pilocarpine to induce status epilepticus (SE). Twenty-four hours after SE, rats underwent perfusion/fixation and their brains were processed for hippocampal neuronal injury. Some rats were housed for longer periods and monitored for evidence of spontaneous seizures. Results: P17 pups that experienced FPI followed by SE demonstrated similar numbers of injured neurons in the CA1 and CA3 regions, as did shams that were subjected to SE. However, the number of injured neurons in the hilus of injured rats after SE exceeded those of the sham (12.2 ± 3.6 vs.3.4 ± 1.4). Conclusions: Our data suggest that even in the absence of overt histological damage, TBI to the immature brain causes neuronal dysfunction resulting in increased vulnerability to a secondary injury (seizures). These findings may provide a mechanistic connection between EPTS and the long-term development of epilepsy and may emphasize the need for effective anticonvulsant and neuroprotective strategies in the management of TBI.