EARLY NEUROPATHOLOGIC EFFECTS OF MILD OR MODERATE HYPOXEMIA AFTER CONTROLLED CORTICAL IMPACT INJURY IN RATS

Hypoxemia has detrimental effects after traumatic brain injury (TBI) i n both experimental models and humans. The purpose of this study was t o determine the effect of mild or moderate hypoxemia on early histolog ic and motor functional outcome after controlled cortical impact (CCI) in rats. Anesthetized rats under,vent CCI and were randomized to rece ive mild (FiO(2) = 13%, n = 6), moderate (FiO(2) = 11%, n = 9), or no (FiO(2) = 33%, n 6) hypoxemia for 30 min after trauma. Sham-operated r ats without hypoxemia (n = 7) were used as controls. Motor function (b eam balance latency) was assessed on days 0-5. Rats were killed 7 days after injury and their brains removed for assessment of survival of h ippocampal neurons and contusion volume. Terminal deoxynucleotidyl tra nsferase-mediated biotin-dUTP nick end labeling (TUNEL) was performed on brain sections from rats killed at 6, 24, and 72 h after CCI and mo derate hypoxemia to assess DNA fragmentation irt situ. Mild and modera te hypoxemia augmented motor function deficits after CCI in a dose-dep endent manner. Moderate hypoxemia after CCI reduced 7-day survival of CA3 neurons but not CA1 neurons vs. sham (55 [46-86] vs. 99 [95-130], p < 0.05, and 79 [63-86] vs. 101 [81-123], NS, respectively; % uninjur ed hemisphere, median [range]). The addition of mild or moderate hypox emia did not increase contusion volume. TUNEL-positive neurons were se en in ipsilateral cortex and dentate gyrus at 6, 24, and 72 h after tr auma, and in ipsilateral CA3 hippocampal neurons and thalamus at 24 an d 72 h. Moderate hypoxemia augments CA3 neuronal death and early motor functional deficits after CCI. The pattern of DNA fragmentation in se lectively vulnerable neurons suggests that apoptosis may play a role i n the delayed neuronal death seen after TBI.