Be. Levin et al., CHRONIC ALTERATIONS IN RAT-BRAIN ALPHA-ADRENOCEPTORS FOLLOWING TRAUMATIC BRAIN INJURY, Restorative neurology and neuroscience, 7(1), 1994, pp. 5-12
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.