Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats.
Hypoxemia has detrimental effects after traumatic brain injury (TBI) in both experimental models and humans. The purpose of this study was to determine the effect of mild or moderate hypoxemia on early histologic and motor functional outcome after controlled cortical impact (CCI) in rats. Anesthetized rats underwent CCI and were randomized to receive mild (FiO2 = 13%, n = 6), moderate (FiO2 = 11%, n = 9), or no (FiO2 = 33%, n = 6) hypoxemia for 30 min after trauma. Sham-operated rats without hypoxemia (n = 7) were used as controls. Motor function (beam balance latency) was assessed on days 0-5. Rats were killed 7 days after injury and their brains removed for assessment of survival of hippocampal neurons and contusion volume. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) was performed on brain sections from rats killed at 6, 24, and 72 h after CCI and moderate hypoxemia to assess DNA fragmentation in situ. Mild and moderate hypoxemia augmented motor function deficits after CCI in a dose-dependent 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; % uninjured hemisphere, median [range]). The addition of mild or moderate hypoxemia did not increase contusion volume. TUNEL-positive neurons were seen in ipsilateral cortex and dentate gyrus at 6, 24, and 72 h after trauma, and in ipsilateral CA3 hippocampal neurons and thalamus at 24 and 72 h. Moderate hypoxemia augments CA3 neuronal death and early motor functional deficits after CCI. The pattern of DNA fragmentation in selectively vulnerable neurons suggests that apoptosis may play a role in the delayed neuronal death seen after TBI.
Clark
R S
RS
Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
Kochanek
P M
PM
Dixon
C E
CE
Chen
M
M
Marion
D W
DW
Heineman
S
S
DeKosky
S T
ST
Graham
S H
SH
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D001930:Brain Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D002470:Cell Survival; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology*; D053938:DNA Fragmentation; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity; D009474:Neurons / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley