TRAUMATIC BRAIN INJURY ALTERS SYNAPTIC HOMEOSTASIS - IMPLICATIONS FORIMPAIRED MITOCHONDRIAL AND TRANSPORT FUNCTION

This study utilized a unilateral controlled cortical impact model of t raumatic brain injury to assess disruptions of synaptic homeostasis fo llowing trauma. Adult rats were subjected to a moderate (2 mm) cortica l deformation and synaptosomes were prepared from the entire ipsilater al (injured) hemisphere or dissected into different regions (hippocamp us, injured cortical area including penumbra, residual hemisphere) at various times postinjury (10 and 30 min, and 1, 6, and 24 h), Synaptos omes from the corresponding regions of the contralateral hemisphere we re used as controls to assess alterations in synaptic ATP levels, lipi d peroxidation, and glutamate and glucose transport. The results demon strate significant time-dependent alterations in synaptic homeostasis, which included an immediate reduction in ATP levels, coupled with a s ignificant increase in lipid peroxidation within 30 min postinjury, Li pid peroxidation demonstrated a biphasic response with elevations obse rved 24 h postinjury, a time at which decreases in glutamate and gluco se transport occurred. These results suggest that disruption of synapt ic homeostasis is an extremely early event following trauma that shoul d be considered when designing pharmacological interventions.