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Progesterone: protective effects on the cat hippocampal neuronal damage due to acute global cerebral ischemia
M D González-Vidal1, M Cervera-Gaviria, R Ruelas
1Unidad de Investigación Médica en Farmacología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), México, D.F.
Background:
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.
Methods:
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.
Results:
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%).
Conclusions:
Overall results suggest that progesterone exerts protective effects against the neuronal cerebral damage induced by acute global cerebral ischemia.