Title:Inhibition of Brain Ischemia-Caused Notch Activation in Microglia May Contribute to Isoflurane Postconditioning-Induced Neuroprotection in Male Rats
VOLUME: 13 ISSUE: 4
Author(s):Jinbo Yin, Hong Li, Chenzhuo Feng and Zhiyi Zuo
Affiliation:Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, Virginia 22908-0710, USA.
Keywords:Apoptosis, focal brain ischemia, isoflurane, microglia, Notch, postconditioning.
Abstract:Prolonged exposure to volatile anesthetics alone may be detrimental to the brain. However, volatile anesthetics,
such as isoflurane, can provide neuroprotection against various damaging insults. Application of isoflurane after focal
brain ischemia reduces ischemic brain injury. We determined whether this isoflurane postconditioning-induced
neuroprotection requires inhibition of brain ischemia-induced Notch signaling activation. Here, we showed that TUNELpositive
staining cell density and active caspase 3 expression were increased in the ischemic penumbral brain tissues of
male rats after a 90-min middle cerebral arterial occlusion (MCAO). This increase was inhibited by isoflurane
postconditioning and a Notch inhibitor. Isoflurane postconditioning and the Notch inhibitor also inhibited brain ischemiainduced
Notch activation and proinflammatory cytokine production. Most cells expressing active Notch also were positive
for CD11b, a microglial and white blood cell marker. Isoflurane postconditioning and the Notch inhibitor inhibited 1
ng/ml lipopolysaccharide- and oxygen-glucose deprivation-induced Notch activation and proinflammatory cytokine
production from microglial cultures. The inhibition of cytokine production by isoflurane postconditioning, but not by a
high concentration of the Notch inhibitor, disappeared in the presence of 10 ng/ml lipopolysaccharide. Our results suggest
that Notch activation in microglia contributes to the cell apoptosis in the ischemic brain tissues. Inhibiting this Notch
activation may participate in isoflurane postconditioning-induced neuroprotection against transient focal brain ischemia in
male rats.
