Effects of 17β-Estradiol on Blood-Brain Barrier Disruption During Focal Ischemia in Rats

Abstract

This study was performed to test whether 17beta-estradiol could attenuate the blood-brain barrier disruption caused by middle cerebral artery occlusion in the ovariectomized rats. Rats aged twelve to fourteen weeks were used in this study. Their ovaries were removed one week prior to the implantation of the pellets. For the 17beta-estradiol group, a 500 microg 17beta-estradiol 21 day-release pellet was implanted and for the control group, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion under isoflurane anesthesia, the transfer coefficient of 14C-alpha-aminoisobutyric acid (104 Daltons) and the volume of 3H-dextran (70,000 Daltons) distribution were determined to represent the degree of blood-brain barrier disruption. Blood pressures and blood gases were similar between controls and 17beta-estradiol-treated rats. In both groups, the transfer coefficient of the ischemic cortex was higher than that of the corresponding contralateral cortex (control: Ischemic Cortex 12.5 +/- 5.9 microl/g/min, Contralateral Cortex 3.0 +/- 1.6, p < 0.001; 17beta-estradiol: Ischemic Cortex 6.7 +/- 3.3 micro l/g/min, Contralateral Cortex 2.2 +/- 0.9, p < 0.01). There was no significant difference in the transfer coefficient of the contralateral cortex between these two groups. However, the transfer coefficient of the Ischemic Cortex of the 17beta-estradiol-treated animals was 46 % lower than that of the control, vehicle-treated rats (p < 0.05). The increase of the volume of 3H-dextran distribution with middle cerebral artery occlusion was significant in the vehicle-treated rats (Ischemic Cortex: 6.4 +/- 2.7 ml/100 g, Contralateral Cortex: 3.8 +/- 0.8, p < 0.01) but not in the 17beta-estradiol-treated animals. Our data suggest that chronic 17beta-estradiol treatment was effective in reducing blood-brain barrier disruption during focal ischemia in the ovariectomized rats.

Effects of Erythropoietin on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia

“…The degree of disruption can vary depending on many factors such as the size of molecules of the tracers, methods of MCA occlusion, duration of occlusion, blood pressure, gender, anesthetics and species [1,[15][16][17] . In this study there was no difference in experimental conditions and vital signs between these two groups.…”

The neurotrophin receptor p75NTR mediates early anti-inflammatory effects of estrogen in the forebrain of young adult rats

“…The present study indicates that estrogen exploits p75NTR-dependent anti-inflammatory mechanisms, and that this action may also occur at the blood brain barrier. In fact, estrogen itself is known to reduce transport across the blood brain barrier in injured [55,56] and non-injured animals [33] and reduces monocyte migration into the brain following ischemia [6]. …”

Alzheimer's Factors in Ischemic Brain Injury

“…after ischemic brain injury (Kiryk et al, 2011). Most scientists have taken the approach of studying estrogen effects on pathology related to ageing disorders (Simpkins et al, 1997;Dubal et al, 1998;Shi et al, 1998;Chi et al, 2002;Chi et al, 2005). Estrogens exert protective activity in animals ischemic brain injury (Simpkins et al, 1997;Dubal et al, 1998;Shi et al, 1998;Chen et al, 2001;Chi et al, 2002;, but the mechanisms of their protection are not understood.…”

“…Estrogens exert protective activity in animals ischemic brain injury (Simpkins et al, 1997;Dubal et al, 1998;Shi et al, 1998;Chen et al, 2001;Chi et al, 2002;, but the mechanisms of their protection are not understood. These hormones may guard neuronal integrity ) by readjusting the physiological activity of the blood-brain barrier (Chi et al, 2002;Chi et al, 2005). Another probable mechanism is that estrogens decreases overexpression of amyloid precursor protein messenger RNA in ischemic brain injury (Shi et al, 1998).…”