TRAUMATIC BRAIN INJURY EXACERBATES SEIZURE-INDUCED DAMAGE IN THE HILUS OF RAT PUPS
Abstract number :
2.095
Submission category :
Year :
2003
Submission ID :
4028
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Raman Sankar, Elisa R. Zanier, Don Shin, David Hovda, Christopher C. Giza Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA; Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA; Neurology, David Geffen School of Medic
Early post-traumatic seizures (EPTS) occur in humans, and are more common in the pediatric population. Sequelae of TBI in humans include epilepsy, memory disturbances and cognitive problems. 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.
P17 rat pups, pretreated with 3mEq/kg LiCl, were anesthetized using isoflurane and implanted with a skull cap filled with saline. Rats were then subjected to moderate lateral FPI injury using loss of consciousness and responsivity to toe pinch as criteria for injury severity. One hour after FPI or sham treatment, rats were given 60mg/kg pilocarpine to induce status epilepticus (SE). 24hr after induction of SE, rats underwent perfusion/fixation and their brains were processed for routine examination with hematoxylin/eosin for hippocampal neuronal injury. Injured neurons were visualized under fluorescence as described by us previously.
The P17 pups that underwent FPI demonstrated similar numbers of injured neurons in the CA1 and CA3 regions of the hippocampus after LiPC-SE as those that did not experience FPI. However, in the hilus of the hippocampus, the number of injured hilar neurons in pups subjected to SE after FPI exceeded that in the sham-treated (12.2 [plusmn] 3.6* vs. 3.4 [plusmn] 1.4).
Our data supports the concept 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). Hippocampal hilar injury and resulting plastic changes in circuitry such as mossy fiber sprouting may be important factors that contribute to epileptogenicity and persistent cognitive deficits. 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.
[Supported by: DAPA Foundation, UCLA Brain Injury Research Center and NINDS (NS27544, NS02197).]