Xiaodong Deng1, Chong Liang2, Lei Qian1, Qi Zhang3. 1. Department of Neurosurgery, The First Affiliated Hospital of China Naval Medical University Shanghai City, China. 2. Department of Neurosurgery, Jinling Hospital, Nanjing University School of Medicine Nanjing, Jiangsu Province, China. 3. Department of Cerebrovascular Diseases, Brain Hospital Affiliated to Tongji University Shanghai City, China.
Abstract
OBJECTIVE: To investigate the effects of miR-24 and HMOX1 on the inflammatory response and neurological function in rats with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Fifteen Sprague-Dawley rats were randomly assigned to the sham group (sham operation, treated with normal saline). Rat model of SAH-induced CVS was established in 90 rats, and these rats were randomly divided into the model, miR-24 NC (treated with miR-24-NC vector), miR-24 inhibitor (treated with miR-24 inhibitor vector), HMOX-NC (treated with HMOX1-NC vector), oe-HMOX1 (treated with HMOX1 overexpression vector), and miR-24 inhibitor + si-HMOX1 (treated with miR-24 inhibitor and si-HMOX1 vectors) groups. Adenoviral vectors containing the target sequences were injected into the hippocampus of the rats in the corresponding groups. Dual-luciferase reporter assay was conducted to verify the relationship between miR-24 and HMOX1. The learning and memory abilities, neurological function, cerebral edema, permeability of blood-brain barrier, myeloperoxidase activity, and levels of miR-24, HMOX1, interleukin-6, tumor necrosis factor-α, superoxide dismutase, and malondialdehyde in rats were examined. RESULTS: miR-24 could negatively regulate HMOX1 expression. SAH-induced CVS was accompanied with increased miR-24 expression and decreased HMOX1 expression. Inhibiting miR-24 expression or enhancing the expression of its down streaming target, HMOX1, could partly reverse the increased oxidation and inflammation as well as functional deficits in the rats. Moreover, the effects of miR-24 inhibitor could be reversed by inhibiting HMOX1 expression. CONCLUSION: miR-24 downregulation can promote HMOX1 expression, thereby decreasing the inflammatory response and improving the neurological function of rats with CVS after SAH. AJTR
OBJECTIVE: To investigate the effects of miR-24 and HMOX1 on the inflammatory response and neurological function in rats with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Fifteen Sprague-Dawley rats were randomly assigned to the sham group (sham operation, treated with normal saline). Rat model of SAH-induced CVS was established in 90 rats, and these rats were randomly divided into the model, miR-24 NC (treated with miR-24-NC vector), miR-24 inhibitor (treated with miR-24 inhibitor vector), HMOX-NC (treated with HMOX1-NC vector), oe-HMOX1 (treated with HMOX1 overexpression vector), and miR-24 inhibitor + si-HMOX1 (treated with miR-24 inhibitor and si-HMOX1 vectors) groups. Adenoviral vectors containing the target sequences were injected into the hippocampus of the rats in the corresponding groups. Dual-luciferase reporter assay was conducted to verify the relationship between miR-24 and HMOX1. The learning and memory abilities, neurological function, cerebral edema, permeability of blood-brain barrier, myeloperoxidase activity, and levels of miR-24, HMOX1, interleukin-6, tumor necrosis factor-α, superoxide dismutase, and malondialdehyde in rats were examined. RESULTS:miR-24 could negatively regulate HMOX1 expression. SAH-induced CVS was accompanied with increased miR-24 expression and decreased HMOX1 expression. Inhibiting miR-24 expression or enhancing the expression of its down streaming target, HMOX1, could partly reverse the increased oxidation and inflammation as well as functional deficits in the rats. Moreover, the effects of miR-24 inhibitor could be reversed by inhibiting HMOX1 expression. CONCLUSION:miR-24 downregulation can promote HMOX1 expression, thereby decreasing the inflammatory response and improving the neurological function of rats with CVS after SAH. AJTR
Authors: Lars Maegdefessel; Joshua M Spin; Uwe Raaz; Suzanne M Eken; Ryuji Toh; Junya Azuma; Matti Adam; Futoshi Nakagami; Futoshi Nagakami; Helen M Heymann; Ekaterina Chernogubova; Ekaterina Chernugobova; Hong Jin; Joy Roy; Rebecka Hultgren; Kenneth Caidahl; Sonja Schrepfer; Anders Hamsten; Per Eriksson; Michael V McConnell; Ronald L Dalman; Philip S Tsao Journal: Nat Commun Date: 2014-10-31 Impact factor: 14.919