González-Vidal M D, Cervera-Gaviria M, Ruelas R, Escobar A, Moralí G, Cervantes M
Unidad de Investigación Médica en Farmacología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), México, D.F.
Arch Med Res. 1998 Summer;29(2):117-24.
Barbiturates, benzodiazepines, and synthetic steroids having anesthetic properties, by enhancing the inhibitory GABAergic neurotransmission to the neuronal circuits of cerebral structures vulnerable to ischemia, reduce the damage induced by this condition. Some endogenous steroids resulting from progesterone (P4) biotransformation in the brain exert GABAergic effects, thus inhibiting neuronal excitability. Hence, P4 administration both before and after an experimentally induced ischemic episode may prevent or decrease the ischemic cerebral damage.
Ovariectomized adult cats were treated s.c. with either P4 (10 mg/kg/day) or corn oil during 7 days before and 7 days after being subjected to a period of acute global cerebral ischemia by 15 min of cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of survival, animals were sacrificed and the brains perfused in situ and formalin-fixed for histological examination.
Acute global cerebral ischemia resulted in a severe loss of neurons (54-85%), mainly in CA1 and CA2 subfields of oil-treated cats. Progesterone significantly reduced the neuronal loss in those areas (21-49%).
Overall results suggest that progesterone exerts protective effects against the neuronal cerebral damage induced by acute global cerebral ischemia.
具有麻醉特性的巴比妥类、苯二氮卓类和合成类固醇,通过增强对易受缺血影响的脑结构神经元回路的抑制性γ-氨基丁酸能神经传递,减少这种情况引起的损伤。大脑中由孕酮(P4)生物转化产生的一些内源性类固醇具有γ-氨基丁酸能作用,从而抑制神经元兴奋性。因此,在实验性诱导的缺血发作之前和之后给予P4可能预防或减少缺血性脑损伤。
对成年去卵巢猫在经历15分钟心肺骤停继以4分钟复苏的急性全脑缺血期之前7天和之后7天,皮下注射P4(10mg/kg/天)或玉米油。存活14天后,处死动物,原位灌注大脑并固定于福尔马林中用于组织学检查。
急性全脑缺血导致严重的神经元丢失(54%-85%),主要发生在接受玉米油处理的猫的CA1和CA2亚区。孕酮显著减少了这些区域的神经元丢失(21%-49%)。
总体结果表明,孕酮对急性全脑缺血诱导的神经元脑损伤具有保护作用。