BACKGROUND/AIMS: Remote ischemic preconditioning (RIPC) has protective effects on spinal cord ischemia reperfusion (I/R) injury, but the potential mechanisms remain unclear. In our study, the effects and underlying mechanisms of RIPC on blood-spinal cord barrier (BSCB) breakdown following I/R injury were investigated. METHODS: animals underwent intraperitoneal administration with cannabinoid-1 (CB1) receptor antagonist AM251, cannabinoid-2 (CB2) receptor antagonist AM630 or vehicle 15 minutes before three 3-minute occlusion-reperfusion cycles on the right femoral artery or a sham operation. 30 minutes after the preconditioning, aortic arch was exposed with or without 14-minute occlusion. Neurological function was assessed with Tarlov scoring system. The disruption of BSCB was assessed by measuring Evans Blue (EB) extravasation. The expression of tight junction protein occludin was determined by western blot analyses. The expression and localization of CB1 and CB2 receptors were assessed by western blot and immunofluorescence. RESULTS: RIPC attenuated the motor dysfunction, BSCB disruption and downregulation of occludin after I/R injury, which were impaired by blocking CB1 and CB2 receptors. Moreover, RIPC upregulated the elevated perivascular expression of CB1 and CB2 receptors following I/R injury. CONCLUSIONS: These results indicated that RIPC, through activation and upregulation of CB1 and CB2 receptors, was involved in preserving the integrity of BSCB after spinal cord I/R injury.
BACKGROUND/AIMS: Remote ischemic preconditioning (RIPC) has protective effects on spinal cord ischemia reperfusion (I/R) injury, but the potential mechanisms remain unclear. In our study, the effects and underlying mechanisms of RIPC on blood-spinal cord barrier (BSCB) breakdown following I/R injury were investigated. METHODS: animals underwent intraperitoneal administration with cannabinoid-1 (CB1) receptor antagonist AM251, cannabinoid-2 (CB2) receptor antagonist AM630 or vehicle 15 minutes before three 3-minute occlusion-reperfusion cycles on the right femoral artery or a sham operation. 30 minutes after the preconditioning, aortic arch was exposed with or without 14-minute occlusion. Neurological function was assessed with Tarlov scoring system. The disruption of BSCB was assessed by measuring Evans Blue (EB) extravasation. The expression of tight junction protein occludin was determined by western blot analyses. The expression and localization of CB1 and CB2 receptors were assessed by western blot and immunofluorescence. RESULTS: RIPC attenuated the motor dysfunction, BSCB disruption and downregulation of occludin after I/R injury, which were impaired by blocking CB1 and CB2 receptors. Moreover, RIPC upregulated the elevated perivascular expression of CB1 and CB2 receptors following I/R injury. CONCLUSIONS: These results indicated that RIPC, through activation and upregulation of CB1 and CB2 receptors, was involved in preserving the integrity of BSCB after spinal cord I/R injury.
Authors: Faheem I Bhatti; Oliver D Mowforth; Max B Butler; Aniqah I Bhatti; Sylva Adeeko; Melika Akhbari; Rory Dilworth; Ben Grodzinski; Temidayo Osunronbi; Luke Ottewell; Jye Quan Teh; Sophie Robinson; Gayathri Suresh; Unaiza Waheed; Benn Walker; Isla Kuhn; Lara Smith; Richard D Bartlett; Benjamin M Davies; Mark R N Kotter Journal: Spinal Cord Date: 2021-08-14 Impact factor: 2.772