Progesterone as A Neuroprotective Treatment in Brain Ischemic Injury in Ovariectomized Rats: Relation to Brain Derived Neurotrophic Factor, Synaptic Plasticity and Astrocytes
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- Category: Vol. 80, September 2012
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Progesterone as A Neuroprotective Treatment in Brain Ischemic Injury in Ovariectomized Rats: Relation to Brain Derived Neurotrophic Factor, Synaptic Plasticity and Astrocytes,NAGAT YOUNAN, SAMAH EL-ATTAR and DINA SABRY
Abstract
Background: Ischemic brain injuries are a global health problem. Epidemiological studies have shown that stroke incidence and mortality rates are higher in men relative to age-matched women worldwide, suggesting that stroke is a sexually dimorphic disease. Although cardioprotection has been reported with postmenopausal estrogen or estrogen-progestin replacement, a limited number of epidemiologic studies have evaluated progestins and stroke risk.
Aim of the Work: To investigate a possible neuroprotective effect of exogenous progesterone administration in young adult ovariectomized female rats subjected to bilateral common carotid artery ligation (BCCAL). Also the role of PROG administered either before or after the start of experimentally induced brain ischemia in modulating gene expression of brain derived neurotrophic factor (BDNF), synaptophysin as a presynaptic marker to synaptic plasticity and astrocytic function as indicated by measuring glial fibrillary acid protein (GFAP) was evaluated in this study.
Methodology: 50 female rats were divided into 5 groups, each group was composed of 10 rats, 4 groups underwent ovariectomy, and one group was designed to be the control group. Group 1: Normal rats (NOR), served as normal control. Group 2: Ovariectomy group (OVX) rats of this group under-went ovariectomy operation. Group 3: Ovariectomiezed rats and underwent bilateral common carotid artery ligation (BC-CAL). Group 4: Ovariectomized rats, underwent BCCAL, and received intraperitoneal injection (i.p.) of progesterone in a dose of 16 mg/kg BW 30 minutes before BCCAL and Group 5: Ovariectomized rats, underwent BCCAL and received i.p. progesterone in a dose of 15mg/kg one hour after permanent BCCAL. Two weeks after ovariectomy, bilateral common carotid arteries were ligated. In all the included animals, measurements of percent of infarct area in brain and brain oedema and quantitative gene expression of BDNF, GFAP and synaptophysin were estimated in animals 24hours after BCCAL.
Results: BCCAL significantly increased brain water content and infarct area in ovariectomized rats compared to control animals (normal). Progesterone treatment 30min before or 1hr after BCCAL significantly reduced water content and infarct area in rat brains compared with the ischemic untreated ovariectomized rats. BDNF, synaptophysin and GFAP gene expression was significantly elevated in the brain tissues in rats exposed to BCCAL compared with ovariectomized rats (p<0.05) and that PROG administration whether before or after the start of ischemia significantly increased the expression of BDNF and synaptophysin and significantly decreased the expression of GFAP in PROG treated ischemic rats compared with untreated ischemic rats (p<0.05).
Conclusion: This study provides an evidence that the PROG treatment before or after stroke protected the brain against ischemic injury as demonstrated by decreasing infarct area and oedema and suppresses ischemia-stimulated prolif-eration of scar tissues but stimulates growth of neurons and synaptic tissues through enhancement of expression of the neurotrophic factor BDNF and synaptic proteins.