Acute etomidate treatment reduces cognitive deficits and histopathology in rats with traumatic brain injury.
OBJECTIVE
To test the hypothesis that etomidate treatment improves functional, cognitive, and histologic outcome after experimental traumatic brain injury.


METHODS
Controlled animal study.


METHODS
University research laboratory.


METHODS
Male Sprague-Dawley rats.


METHODS
Traumatic brain injury was produced by controlled cortical impact injury (4 m/sec, 2.6 mm of tissue deformation). Etomidate (2 mg/kg) was administered intravenously immediately before injury (n = 13) or 5 mins after injury (n = 12). Additional rats received saline treatment 5 mins after injury (n = 12) or served as sham controls (n = 10).


RESULTS
Rats were evaluated on beam balance and beam walk tasks on postoperative days 1-5 and then trained in the Morris water maze on postoperative days 14-18. On day 28, the rats were killed, and hippocampal CA1 and CA3 neuron counts and cortical lesion volume were measured in histologic brain sections. Preinjury etomidate attenuated beam balance deficits, water maze deficits, hippocampal CA3 neuronal loss, and cortical tissue loss but did not attenuate beam walk deficits or hippocampal CA1 neuronal loss. Postinjury etomidate attenuated water maze deficits, but it did not affect any other outcome measure.


CONCLUSIONS
Administration of etomidate both before and after injury attenuates secondary injury resulting from traumatic brain injury, but the effect is more pronounced with pretreatment. The ineffectiveness of postinjury etomidate on motor and histologic tasks suggests a brief therapeutic treatment window in rats. However, the treatment window in humans is unknown. Lastly, postinjury etomidate did not exacerbate neurologic or histologic outcome.
Dixon
C Edward
CE
Department of Neurological Surgery and Safar Center for Resuscitation Research, University of Pittsburgh, PA 15260, USA. ecdixon@msx.upmc.edu
Ma
Xiecheng
X
Kline
Anthony E
AE
Yan
Hong Q
HQ
Ferimer
Howard
H
Kochanek
Patrick M
PM
Wisniewski
Stephen R
SR
Jenkins
Larry W
LW
Marion
Donald W
DW
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D005045:Etomidate / Q000008:administration & dosage / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D006993:Hypnotics and Sedatives; D005045:Etomidate