Long-term effects of post-ischaemic oestrogen on brain injury in a rat transient forebrain ischaemia model

Abstract

The current study was conducted to compare the effects of post-treatment with oestrogen on histological and neurological outcomes after short (7-day) and long (28-day) recovery periods in rats subjected to transient forebrain ischaemia. Male Sprague-Dawley rats were randomly assigned to one of five groups: vehicle (7-day recovery period), vehicle (28-day recovery period), oestrogen (17β-estradiol 200 μg/kg, 7-day), oestrogen (17β-estradiol 200 μg /kg, 28-day), or sham surgical (n = 8 in each group). After forebrain ischaemia was induced with bilateral carotid artery occlusion and haemorrhagic hypotension (mean arterial pressure = 40 mmHg) for 10 min, the brain was reperfused for 7 or 28 days. Either 17β-estradiol or vehicle was injected intravenously during the initial 2 min of reperfusion. To evaluate histological damage, the number of intact neurons per 1 mm in the hippocampal CA1 subfield was counted at 7 or 28 days after transient forebrain ischaemia. At 7 days after ischaemia, the number of intact neurons in the hippocampal CA1 subfield was significantly greater in the oestrogen group [57.5 (46.5)/mm: median (interquartile range)] than in the vehicle group [10 (19.5) /mm; P = 0.014]. However, there was no difference between groups at 28 days after ischaemia [vehicle: 11 (20)/mm vs. oestrogen: 6 (11)/mm]. The neurological deficit scores in the oestrogen and vehicle groups were not different from the sham group at any point post-ischaemia. The current study indicates that post-ischaemic administration of oestrogen provided short-term but not long-term neuroprotective effects in transient forebrain ischaemia in rats.