TY - JOUR AB - Ischemic stroke seriously threatens human health and creates a large social burden. The present study investigated whether tissue inhibitor of metalloproteinases‑3 (TIMP3) prevented cerebral ischemia/reperfusion (I/R), with the aim to explore the underlying mechanism. A transient middle cerebral artery occlusion model was conducted in mice, and oxygen glucose deprivation and reoxygenation (OGD/R) was investigated in PC12 cells to mimic cerebral ischemia‑reperfusion injury (CIRI). Western blotting was used to determine the expression of TIMP3, Bax, Bcl‑2 and AKT. TUNEL was used to detect apoptosis in cerebral tissues or cultured PC12 cells. Expression levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected to reveal oxidative stress. The results demonstrated that TIMP3 expression was significantly decreased after I/R in vivo or OGD/R in vitro, and the number of TUNEL‑positive cells was reduced by the overexpression of TIMP3. The attenuation of Bax/Bcl‑2 ratio in OGD/R‑induced PC12 cells suppressed the expression levels of ROS and MDA; while also elevating SOD activity in the OGD/R‑induced neurocytes in vitro. In addition, TIMP3‑overexpression reversed the downregulation of phosphorylated‑AKT (Thr308 and Ser473) in OGD/R‑treated PC12 cells. However, the anti‑apoptotic and anti‑oxidative stress roles of TIMP3 in OGD/R‑induced PC12 cells were partially abolished after treatment with the AKT inhibitor, AZD5363. Overall, TIMP3 exerted an anti‑apoptotic and anti‑oxidative stress role in CIRI through the AKT pathway, which may be a potential therapeutic target for the treatment of CIRI. AD - Department of Imaging, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China Department of Imaging, Xingtai Orthopedic Hospital, Xingtai, Hebei 054001, P.R. China Department of Cardiothoracic Surgery, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China Department of Neurology, Xingtai People's Hospital, Xingtai, Hebei 054001, P.R. China AU - Meng,Linglei AU - Zhang,Yongting AU - Li,Demao AU - Shang,Xinfang AU - Hao,Xuejia AU - Chen,Xin AU - Gao,Fengxiao DA - 2021/09/01 DO - 10.3892/etm.2021.10405 IS - 3 JO - Exp Ther Med KW - cerebral ischemia‑reperfusion injury tissue inhibitor of metalloproteinases‑3 AKT pathway oxidative stress TUNEL PY - 2021 SN - 1792-0981 1792-1015 SP - 973 ST - TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway T2 - Experimental and Therapeutic Medicine TI - TIMP3 attenuates cerebral ischemia/reperfusion‑induced apoptosis and oxidative stress in neurocytes by regulating the AKT pathway UR - https://doi.org/10.3892/etm.2021.10405 VL - 22 ER -