BACKGROUND/AIMS: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R) injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal cord I/R injury. METHODS: Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. RESULTS: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. CONCLUSIONS: Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.
BACKGROUND/AIMS: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R) injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal cord I/R injury. METHODS:Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. RESULTS: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. CONCLUSIONS:Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.
Authors: Epiphani C Simmons; Natalie E Scholpa; Kristan H Cleveland; Rick G Schnellmann Journal: J Pharmacol Exp Ther Date: 2019-11-27 Impact factor: 4.030
Authors: Necmiye Şengel; Zeynep Köksal; Ali Doğan Dursun; Ömer Kurtipek; Şaban Cem Sezen; Mustafa Arslan; Mustafa Kavutçu Journal: Drug Des Devel Ther Date: 2022-07-13 Impact factor: 4.319