EFFECTS OF MODERATE, CENTRAL FLUID PERCUSSION TRAUMATIC BRAIN INJURY ON NITRIC-OXIDE SYNTHASE ACTIVITY IN RATS

Experimental traumatic brain injury (TBI) damages cerebral vascular en dothelium and reduces cerebral blood flow (CBF), The nitric oxide synt hase (NOS) substrate, L-arginine, prevents CBF reductions after TBI, b ut the mechanism is not known. This study examined the possibility tha t posttraumatic hypoperfusion is due to reductions in the substrate se nsitivity of NOS which are overcome by L-arginine, Isoflurane-anesthet ized rats were prepared for TBI (midline fluid-percussion, 2.2 atm), s ham-TBI, or no surgery (control), and were decapitated 30 min after in jury or sham injury. The brains were removed and homogenized or minced for measurements of crude soluble or cell-dependent stimulated NOS ac tivity, respectively, Baseline arterial oxygen, carbon dioxide, pH, or hemoglobin levels did not differ among control, sham, or TBI groups. Total cortical soluble NOS activity in TBI-treated rats was not signif icantly different from either untreated or sham groups when 0.45 mu M or 1.5 mu M L-arginine was added. Also, there were no differences in c ell-dependent NOS activity among the three groups stimulated by 300 mu M N-methyl-D-aspartate, 50 mM K+, or 10 mu M ionomycin, These data su ggest that TBI reduces CBF by a mechanism other than altering the subs trate specificity or activation of nNOS.