CHRONIC ALTERATIONS IN RAT-BRAIN ALPHA-ADRENOCEPTORS FOLLOWING TRAUMATIC BRAIN INJURY

Norepinephrine (NE) has been implicated in cerebral plasticity and rec overy of function after brain injury. To examine the status of noradre nergic mechanisms in the brain following traumatic brain injury (TBI), male Sprague-Dawley rats underwent right sensorimotor cortex contusio ns and were observed for the next 30 days for recovery of motor functi on by measurement of the time taken to perform a modified beam walking task. At 30 days, their brains were assayed by receptor autoradiograp hy for alpha(1)- and alpha(2)-adrenoceptor binding with 1 nM [H-3]praz osin and 1 nM [H-3]paraminoclonidine, respectively. One day after cont usion, TBI rats took 60% longer to run the beam than sham-lesioned con trols. Run times were directly proportional (r = 0.784; P = 0.012) to lesion volume determined at 30 days. The motor deficit persisted for 8 days, after which TBI and control rats had similar run times, largely due to increased run times in sham rats. At 30 days, TBI rats had a g eneralized, bilateral decrease in [3H]prazosin binding across all brai n areas read (F[1,13] = 9.23; P = 0.009) with specific 12%-21% decreas es in the cortex contralateral to the lesion and bilaterally in the do rsomedial hypothalamic and three thalamic nuclei. On the other hand, [ H-3]paraminoclonidine binding did not differ from sham lesion controls in any brain area of TBI rats. Thus, unilateral TBI is followed by wi despread, bilateral changes in alpha(1)-adrenoceptor binding which wou ld leave the animal vulnerable to any factors which reduced the access of NE to its postsynaptic adrenoceptors. This is compatible with the observation that alpha(1)-antagonists and alpha(2)-agonists can transi ently reinstate the motor deficit after recovery has occurred.