OBJECTIVE AND DESIGN: We evaluated the inhibitory effects of progesterone (PROG) on inflammatory response and its influence on the structure of blood-brain barrier in a permanent model of stroke. MATERIAL: One hundred and twenty adult male Sprague-Dawley rats were used in this study. TREATMENTS: PROG was dissolved in 22.5% 2-hydroxypropyl-bcyclodextrin and given in a dose of 15 mg/kg by intraperitoneal injection 1 h after permanent occlusion of middle cerebral artery (pMCAO). Additional injections of 15 mg/kg were administered subcutaneously 6, 24, and 48 h after pMCAO. METHODS: The expression of tumor necrosis factor-alpha (TNF-alpha) and claudin5 was measured by immunohistochemistry and western blot technique. Brain water content was determined by the dry-wet weight method. RESULTS: TNF-alpha were increased, but claudin5 were reduced in vehicle-treated rats after pMCAO. PROG-treated rats showed a substantial reduction in the expression of TNF-alpha compared to vehicle controls. In addition, there was significant increase in the expression of claudin5 in the pMCAO rats treated with PROG compared to vehicle. Examination of the water content of the brain also revealed that administration of PROG significantly attenuated the amount of water compared to vehicle in the ipsilateral hemispheres. CONCLUSIONS: These data indicate that PROG is beneficial in this animal model, and may warrant further test in future clinical trials for human stroke.
OBJECTIVE AND DESIGN: We evaluated the inhibitory effects of progesterone (PROG) on inflammatory response and its influence on the structure of blood-brain barrier in a permanent model of stroke. MATERIAL: One hundred and twenty adult male Sprague-Dawley rats were used in this study. TREATMENTS: PROG was dissolved in 22.5% 2-hydroxypropyl-bcyclodextrin and given in a dose of 15 mg/kg by intraperitoneal injection 1 h after permanent occlusion of middle cerebral artery (pMCAO). Additional injections of 15 mg/kg were administered subcutaneously 6, 24, and 48 h after pMCAO. METHODS: The expression of tumor necrosis factor-alpha (TNF-alpha) and claudin5 was measured by immunohistochemistry and western blot technique. Brain water content was determined by the dry-wet weight method. RESULTS:TNF-alpha were increased, but claudin5 were reduced in vehicle-treated rats after pMCAO. PROG-treated rats showed a substantial reduction in the expression of TNF-alpha compared to vehicle controls. In addition, there was significant increase in the expression of claudin5 in the pMCAO rats treated with PROG compared to vehicle. Examination of the water content of the brain also revealed that administration of PROG significantly attenuated the amount of water compared to vehicle in the ipsilateral hemispheres. CONCLUSIONS: These data indicate that PROG is beneficial in this animal model, and may warrant further test in future clinical trials for humanstroke.
Authors: M E Meistrell; G I Botchkina; H Wang; E Di Santo; K M Cockroft; O Bloom; J M Vishnubhakat; P Ghezzi; K J Tracey Journal: Shock Date: 1997-11 Impact factor: 3.454