Inhibition of Brain Ischemia-Caused Notch Activation in Microglia May Contribute to Isoflurane Postconditioning-Induced Neuroprotection in Male Rats

Author(s): Jinbo Yin, Hong Li, Chenzhuo Feng, Zhiyi Zuo.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 13 , Issue 4 , 2014

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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.

Keywords: Apoptosis, focal brain ischemia, isoflurane, microglia, Notch, postconditioning.

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2014
Page: [718 - 732]
Pages: 15
DOI: 10.2174/1871527313666140618110837
Price: $58

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