Assessment of postischemic neurogenesis in rats with cerebral ischemia and propofol anesthesia.
BACKGROUND
Postischemic endogenous neurogenesis can be dose-dependently modulated by volatile anesthetics. The intravenous anesthetic propofol is used during operations with a risk of cerebral ischemia, such as neurosurgery, cardiac surgery, and vascular surgery. The effects of propofol on neurogenesis are unknown and, therefore, the object of this study.


METHODS
Eighty male Sprague-Dawley rats were randomly assigned to treatment groups with propofol administration for 3 h: 36 mg x kg(-1) x h(-1) propofol with or without cerebral ischemia and 72 mg x kg(-1) x h(-1) propofol with or without cerebral ischemia. In addition, 7 rats with propofol administration for 6 h and 14 treatment-naive rats were investigated. Forebrain ischemia was induced by bilateral carotid artery occlusion and hemorrhagic hypotension. Animals received 5-bromo-2-deoxyuridine for 7 days. 5-Bromo-2-deoxyuridine-positive neurons were counted in the dentate gyrus after 9 and 28 days. Spatial learning in the Barnes maze and histopathologic damage of the hippocampus were analyzed.


RESULTS
Propofol revealed no impact on basal neurogenesis. Cerebral ischemia increased the amount of new neurons. After 28 days, neurogenesis significantly increased in animals with low-dose propofol administered during cerebral ischemia compared with naive animals, whereas no significant difference was observed in animals with high-dose propofol during ischemia. Neuronal damage in the CA3 region was increased at 28 days with high-dose propofol. Postischemic deficits in spatial learning were not affected by propofol.


CONCLUSIONS
Independent effects of propofol are difficult to ascertain. Peri-ischemic propofol administration may exert secondary effects on neurogenesis by modulating the severity of histopathologic injury and thereby regenerative capacity of the hippocampus.
Lasarzik
Irina
I
Klinik für Anästhesiologie, Johannes Gutenberg-Universität, Mainz, Germany. lasarzik@uni-mainz.de
Winkelheide
Uta
U
Stallmann
Sonja
S
Orth
Christian
C
Schneider
Astrid
A
Tresch
Achim
A
Werner
Christian
C
Engelhard
Kristin
K
D000771:Anesthesia, Intravenous / Q000379:methods; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D015742:Propofol / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015742:Propofol