| Summary: | 碩士 === 國防醫學院 === 生理學研究所 === 97 === Cerebral ischemia / reperfusion (I/R) results in a breakdown of the blood-brain barrier (BBB) which may contribute to brain edema . Aquaporins (AQPs), the water channel proteins linked to water homeostasis, edema and brain blood barrier (BBB) integrity, contribute to secondary ischemic brain injury. They have been found to regulate transmembrane transport of water, glycerol and other small molecules in many organs. Three AQPs (AQP1, AQP4 and AQP9) have been identified in the brain. AQP4 has recently been implicated in the regulation of ion and water homeostasis in I/R.
I/R insult activates autophagy and an autophagic mechanism may contribute to ischemic neuronal injury. The induction of autophagy has also been shown in mouse cortex and striatum after ischemic brain injury.
The administration of granulocyte colony-stimulating factor (G-CSF) after stroke has been shown to decrease infarct volume , enchance angiogenesis and stimulate endogenous neurogenesis.
However, whether G-CSF administration could affect water transport and autophagy after I/R is still unknown.
Using an animal model of focal cerebral ischemia , we examined the effect of subcutaneous administration of G-CSF (200 μg/kg or 50 μg/kg). We examined Western blotting for LC3 and the changes in neurological severity scores, infarct volume, and the mRNA expression of XIAP, AQP1, AQP4, AQP9, MMP9, TIMP1, eNOS, nNOS, iNOS, IL-1b in the penumbra tissues of rats with cerebral I/R .
The administration of G-CSF resulted in the reduced infarct volume, improved neurological scores, down-regulation of AQP1and AQP4 mRNA expression, up-regulation of XIAP、eNOS、nNOS、iNOS and reduced autophagy compared with I/R injury. It also reduced the I/R-induced activation of astrocyte and decreased disruption of BBB. However, we also found that G-CSF increased mRNA expression of IL-1b and MMP9. Taken together, these results suggest that G-CSF can reduce AQP gene expression, astrogliosis, disruption of BBB, and autophagy. G-CSF can shorten the ischemic period by accelerating the recovery of the blood flow. These are new mechanism (s) underlying the protective effects of G-CSF against I/R-induced injury in the brain.
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