Abstracts

Rationale: Traumatic brain injury is a leading cause of acquired epilepsy. At the synaptic level, the mechansims of post-TBI epileptogenesis are not fully understood, but may involve enhancement of excitatory synaptic strength and efficiency that resembles long-tem potentiation (LTP). As a step toward elucidating TBI-related epileptogenic changes, we tested whether transcription of genes related to LTP is increased after injury in a rat severe TBI model. Methods: Materials and Methods: Severe TBI was modeled in adult male Long-Evans rats by a modified lateral fluid percussion (LFP) technique. Severe (3.6 ± 0.3 atm) LFP was delivered over exposed dura after left parietal skull fenestration. A control group underwent skull fenestration, but no LFP. Rats were recovered from TBI for 12 hours (n = 6) and 24 hours (n = 8) before tissue collection. The ipsilesional and contralesional neocortex from each animal was dissected separately, and mRNA from cortical regions was isolated. The mRNA expression was studied by TaqMan quantitative real-time-polymerase chain reaction (qRTPCR), and normalized to the sham TBI control cortex. Among the analyzed transcription products were mRNA levels for B-cell lymphoma protein-2 (Bcl-2), brain-derived neurotrophic factor (BDNF) and CREB binding protein (CBP). Results: 12 hours after TBI, relative to sham TBI control, ipsilesional neocortical tissue exhibited increased expression of the mRNA encoding the injury-related transcription product for Bcl-2 (p < 0.02), which was not significantly elevated in the contralesional cortex (p > 0.1). However, LTP-related BDNF mRNA was increased in the contralesional tissue (p < 0.04) as well as ipsilesional cortex (p < 0.05). 24 hours after TBI, Bcl-2 mRNA remained elevated in the lesional cortex (p < 0.01), where significant increase in LTP-related transcription of BDNF (p < 0.03) and CBP (p < 0.01) mRNA was also found. Conclusions: The present data suggest that LTP-like changes may be triggered by TBI. Notably, increased expression of mRNA transcripts previously reported to be associated with LTP was identified in both lesional and contralesional cortex, suggesting a physiologic effect on synaptic plasticity distal to the immediate site of injury. Further delineation of LTP-like changes after TBI is expected in follow-up experiments.