Hao Zha1, Yaodong Fan2, Li Yang3, Mei Yin4, Wei Miao4, Jin He4, Ying Wang4. 1. Department of Reproductive and Genetics, Second Affiliated Hospital of Kunming Medical University Kunming, China. 2. Department of Neurosurgery, Third Affiliated Hospital of Kunming Medical University Kunming, China. 3. Department of Histology and Embryology, Kunming Medical University Kunming, China. 4. Department of Neurology, Second Affiliated Hospital of Kunming Medical University Kunming, China.
Abstract
OBJECTIVE: To examine the effect of autophagy on cerebral damage caused by different models and test the hypothesis that its protection mechanism acts via inhibiting expression of neuroinflammatory mediators. METHODS: Autophagy was induced by rapamycin treatment. Cerebral damage was induced using models of IL-6 treatment, oxygen glucose deprivation/reoxygenation (OGD/R) in vitro, and middle cerebral artery occlusion (MCAO) in vivo. The effect and mechanism of autophagy was examined and assessed in terms of cell viability, infarction size in brain tissue, neurological score, production of inflammatory mediators IL-1β and IL-6, transcription and protein expression of autophagy markers beclin-1 and LC-3II in different experimental groups. RESULTS: Autophagy triggered by rapamycin could protect neurons from IL-6-induced injury and astrocytes from OGD/R-induced injury in vitro and in rat brain tissue from MCAO in vivo. Autophagy significantly increased cell viability, attenuated cerebral infarction and improved neurological scores. It also inhibited production of the IL-1β and IL-6 and elevated the expression of beclin-1 and LC-3II. CONCLUSIONS: Autophagy can inhibit the inflammatory response and reduce cerebral I/R injury. There was a relationship between the extent of protection and (i) the level of the autophagic response, (ii) the stage of the cerebral I/R injury, and (iii) the time of intervention. AJTR
OBJECTIVE: To examine the effect of autophagy on cerebral damage caused by different models and test the hypothesis that its protection mechanism acts via inhibiting expression of neuroinflammatory mediators. METHODS: Autophagy was induced by rapamycin treatment. Cerebral damage was induced using models of IL-6 treatment, oxygen glucose deprivation/reoxygenation (OGD/R) in vitro, and middle cerebral artery occlusion (MCAO) in vivo. The effect and mechanism of autophagy was examined and assessed in terms of cell viability, infarction size in brain tissue, neurological score, production of inflammatory mediators IL-1β and IL-6, transcription and protein expression of autophagy markers beclin-1 and LC-3II in different experimental groups. RESULTS: Autophagy triggered by rapamycin could protect neurons from IL-6-induced injury and astrocytes from OGD/R-induced injury in vitro and in rat brain tissue from MCAO in vivo. Autophagy significantly increased cell viability, attenuated cerebral infarction and improved neurological scores. It also inhibited production of the IL-1β and IL-6 and elevated the expression of beclin-1 and LC-3II. CONCLUSIONS: Autophagy can inhibit the inflammatory response and reduce cerebral I/R injury. There was a relationship between the extent of protection and (i) the level of the autophagic response, (ii) the stage of the cerebral I/R injury, and (iii) the time of intervention. AJTR