Neuroprotective Effects of Estrogen Treatment on Ischemia-induced Behavioural Deficits in Ovariectomized Gerbils at Different Ages

Although much is known about the protective effect of acute estrogen therapy in cerebral ischemia, relatively little is known about its effect on functional outcome at different ages. The impact of age is, however, important on the efficacy of steroids in the central nervous system. We investigated whether a single dose of estradiol pre-treatment would be neuroprotective in young (4 months), middle-aged (9 months) and old (18 months) female gerbils following 10min global brain ischemia. Apoptotic and necrotic cells were labelled and quantified in the affected hippocampus; exploratory activity, attention and memory functions were tested using open field, spontaneous alternation, novel object recognition and hole-board test. Age effect and treatment effect were analysed. High single dose (4mg/kg b.w.) of estradiol pre-treatment exposed a marked neuroprotective effect against hippocampal cell loss in all age groups. In behavioural tests, however, age-related differences could be observed. In middle-aged and old animals the worsening in memory function following ischemia was more prominent compared to that in the young ones. In the Y-maze and the novel object recognition tests the middle-aged, in the hole-board test (investigating working memory and total time) the old gerbils had the worst functional outcome. Only reference memory in hole-board test did not change by age. Estrogen improved memory performances in all the tests at every age. We can conclude that age of experimental animals is a factor worsening the outcome following brain ischemia. A single-dose estrogen therapy prevents the lesion-induced behavioural dysfunctions and the hippocampal cell loss.