Restoration of cerebral vasoreactivity by an L-type calcium channel blocker following fluid percussion brain injury.

Traumatic brain injury (TBI) results in significant acute reductions in regional cerebral blood flow (rCBF). However, the mechanisms by which TBI impairs CBF and cerebral vascular reactivity have remained elusive. In the present study, the effect of verapamil, an L-type calcium (Ca(2+)) channel blocker, on post-traumatic vascular reactivity was evaluated following a lateral fluid percussion injury (FPI) in rats. rCBF was measured by [(14)C]-iodoantipyrine autoradiography 1 h after FPI. Following FPI, significant rCBF reductions were documented in all examined cortical areas. These reductions were the most prominent (72.0%) at the primary injury site. Intravenous infusion of verapamil (VE; 200 microg/kg/min), and norepinephrine (NE; 20 microg/mL/min) to maintain normal blood pressure, increased rCBF by 141.5% at the primary injury site when compared to untreated, FPinjured animals. Under stimulated conditions, both the ipsilateral and contralateral hemispheres failed to show any increases in rCBF at 1 h following FPI. In direct contrast, following VE+NE treatment all cortical areas measured showed near normal vascular reactivity to direct cortical stimulation (normal reactivity = 45% increase in rCBF vs. 47% increase in FPI+VE+NE cases). These findings suggest that the majority of post-traumatic hemodynamic depressions are closely related to mechanisms involving vasoconstriction. Furthermore, Ca(2+) may play a causative role in this vasoconstriction and the loss of vasoreactivity.