Chi Wang1, Muyang Yan2, Hui Jiang2, Qi Wang3, Shang He1, Jingwen Chen2, Chengbin Wang4. 1. Department of Clinical Laboratory, PLA General Hospital, 100853 Beijing, China. 2. Department of Hyperbaric Chamber, PLA General Hospital, 100853 Beijing, China. 3. Outpatient Department of Chinese People's Liberation Army Aviation School, 101023 Beijing, China. 4. Department of Clinical Laboratory, PLA General Hospital, 100853 Beijing, China. Electronic address: wangcb301301@163.com.
Abstract
AIM: We aim to investigate the mechanism of aquaporin 4 (AQP 4) up-regulation during high-altitude cerebral edema (HACE) in rats under hypobaric hypoxia and preventative effect of puerarin. METHODS: Rats were exposed to a hypobaric chamber with or without the preventative treatment of puerarin or dexamethasone. Morriz water maze was used to evaluate the spatial memory injury. HE staining and W/D ratio were used to evaluate edema injury. Rat astrocytes and microglia were co-cultured under the condition of hypoxia with the administration of p38 inhibitor, NF-κB inhibitor or puerarin. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF α) of cortex and culture supernatant were measured with ELISA. AQP4, phosphorylation of MAPKs, NF-κB pathway of cortex and astrocytes were measured by Western blot. KEY FINDINGS: Weakened spatial memory and cerebral edema were observed after hypobaric hypoxia exposure. AQP4, phosphorylation of NF-κB and MAPK signal pathway of cortex increased after hypoxia exposure and decreased with preventative treatment of puerarin. Hypoxia increased TNF-α and IL-6 levels in cortex and microglia and puerarin could prevent the increase of them. AQP4 of astrocytes increased after co-cultured with microglia when both were exposed to hypoxia. AQP4 showed a decrease after administered with p38 inhibitor, NF-κB inhibitor or puerarin. SIGNIFICANCE: Hypoxia triggers inflammatory response, during which AQP4 of astrocytes can be up regulated through the release of TNF-α and IL-6 from microglia. Puerarin can exert a preventative effect on the increase of AQP4 through inhibiting the release of TNF-α and phosphorylation of NF-κB, MAPK pathway.
AIM: We aim to investigate the mechanism of aquaporin 4 (AQP 4) up-regulation during high-altitude cerebral edema (HACE) in rats under hypobaric hypoxia and preventative effect of puerarin. METHODS:Rats were exposed to a hypobaric chamber with or without the preventative treatment of puerarin or dexamethasone. Morriz water maze was used to evaluate the spatial memory injury. HE staining and W/D ratio were used to evaluate edema injury. Rat astrocytes and microglia were co-cultured under the condition of hypoxia with the administration of p38 inhibitor, NF-κB inhibitor or puerarin. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF α) of cortex and culture supernatant were measured with ELISA. AQP4, phosphorylation of MAPKs, NF-κB pathway of cortex and astrocytes were measured by Western blot. KEY FINDINGS: Weakened spatial memory and cerebral edema were observed after hypobaric hypoxia exposure. AQP4, phosphorylation of NF-κB and MAPK signal pathway of cortex increased after hypoxia exposure and decreased with preventative treatment of puerarin. Hypoxia increased TNF-α and IL-6 levels in cortex and microglia and puerarin could prevent the increase of them. AQP4 of astrocytes increased after co-cultured with microglia when both were exposed to hypoxia. AQP4 showed a decrease after administered with p38 inhibitor, NF-κB inhibitor or puerarin. SIGNIFICANCE: Hypoxia triggers inflammatory response, during which AQP4 of astrocytes can be up regulated through the release of TNF-α and IL-6 from microglia. Puerarin can exert a preventative effect on the increase of AQP4 through inhibiting the release of TNF-α and phosphorylation of NF-κB, MAPK pathway.
Authors: Francesco Pisani; Laura Simone; Maria Grazia Mola; Manuela De Bellis; Antonio Frigeri; Grazia Paola Nicchia; Maria Svelto Journal: Glia Date: 2021-05-26 Impact factor: 7.452