The protective mechanism of progesterone on blood-brain barrier in cerebral ischemia in rats.

Recent studies demonstrate that progesterone (PROG) significantly reduces cerebral edema and enhances functional recovery from traumatic brain injury (TBI) and stroke in several animal models, but its concrete mechanism is still unknown. This study was designed to investigate the inhibitory effects of PROG on inflammatory response after stroke and its influence on the structure of blood-brain barrier (BBB). In the treatment group, PROG was dissolved in 22.5% 2-hydroxypropyl-bcyclodextrin and given in a dose of 8 mg/kg by intraperitoneal injection 1h and 6h after permanent occlusion of middle cerebral artery (pMCAO). Additional injections of 15 mg/kg were administered subcutaneously once a day after pMCAO. The expression of tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9) and claudin5 was measured by western blot technique. Evan's blue extravasation and brain water content in the ipsilateral hemisphere was also detected to evaluate the permeability of BBB. Western blot analysis revealed that the expression of TNF-alpha and MMP-9 were reduced while claudin5 was up-regulated in brain tissues of PROG-treated rats. In addition, examination of BBB permeability also showed that administration of PROG significantly reduced Evan's blue extravasation and brain water content in the ipsilateral hemisphere compared to vehicle-treated rats. Our findings reveal that PROG inhibited the inflammatory response after experimental stroke and mitigated the severity of brain damage, suggesting a role for PROG in the integrity of the BBB and subsequent edema formation following cerebral ischemia.