Traumatic brain injury alters synaptic homeostasis: implications for impaired mitochondrial and transport function.
This study utilized a unilateral controlled cortical impact model of traumatic brain injury to assess disruptions of synaptic homeostasis following trauma. Adult rats were subjected to a moderate (2 mm) cortical deformation and synaptosomes were prepared from the entire ipsilateral (injured) hemisphere or dissected into different regions (hippocampus, injured cortical area including penumbra, residual hemisphere) at various times postinjury (10 and 30 min, and 1, 6, and 24 h). Synaptosomes from the corresponding regions of the contralateral hemisphere were used as controls to assess alterations in synaptic ATP levels, lipid peroxidation, and glutamate and glucose transport. The results demonstrate significant time-dependent alterations in synaptic homeostasis, which included an immediate reduction in ATP levels, coupled with a significant increase in lipid peroxidation within 30 min postinjury. Lipid peroxidation demonstrated a biphasic response with elevations observed 24 h postinjury, a time at which decreases in glutamate and glucose transport occurred. These results suggest that disruption of synaptic homeostasis is an extremely early event following trauma that should be considered when designing pharmacological interventions.
Sullivan
P G
PG
Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA.
Keller
J N
JN
Mattson
M P
MP
Scheff
S W
SW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism; D006706:Homeostasis; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D013997:Time Factors
D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005947:Glucose