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β-Estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil

1997; Elsevier BV; Volume: 29; Issue: 4 Linguagem: Inglês

10.1016/s0168-0102(97)00106-5

1872-8111

Satoko Sudo, Tong‐Chun Wen, Junzo Desaki, Seiji Matsuda, Junya Tanaka, Tatsuru Arai, Nobuji Maeda, Masahiro Sakanaka,

Neurogenesis and neuroplasticity mechanisms

β-Estradiol has been considered to be a neurotrophic agent, but its in vivo effect on gerbils with transient forebrain ischemia has not yet been demonstrated. In the first set of the present experiments, we infused β-estradiol at a dose of 0.05 or 0.25 μg/day for 7 days into the lateral ventricles of normothermic gerbils starting 2 h before 3-min forebrain ischemia. β-Estradiol infusion at a dose of 0.25 μg/day prevented significantly the ischemia-induced reduction of response latency time as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the hippocampal CA1 region as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with β-estradiol than in those receiving saline infusion. β-Estradiol at a dose of 1.25 μg/day was ineffective and occasionally increased the mortality of experimental animals. Since the total brain content of exogenous β-estradiol at 12 h after forebrain ischemia was estimated to be less than 145 ng, the second set of experiments focused on the neurotrophic action of β-estradiol at concentrations around 100 ng/ml in vitro. β-Estradiol at concentrations of 1–100 ng/ml facilitated the survival and process extension of cultured hippocampal neurons, but it did not exhibit any significant radical-scavenging effects at the concentration range. On the other hand, 100 μg/ml of β-estradiol, even though failing to support hippocampal neurons in vitro, effectively scavenged free radicals in subsequent in vitro studies, as demonstrated elsewhere. These findings suggest that β-estradiol at a dose of 0.25 μg/day prevents ischemia-induced learning disability and neuronal loss at early stages after transient forebrain ischemia, possibly via a receptor-mediated pathway without attenuating free radical neurotoxicity.