Post-ischemic administration of progesterone in rats exerts neuroprotective effects on the hippocampus.
Progesterone is neuroprotective in models of focal or global ischemia when treatment starts either before the insult or at the onset of reperfusion. In these cases the steroid may act during the occurrence of the early pathophysiological events triggered by ischemia or reperfusion. As opposed to this condition, the aim of the present study was to assess the effect of delayed, post-injury administration of progesterone on the preservation of pyramidal neurons of the hippocampus of rats 21 days after been exposed to global ischemia by the four vessel occlusion model. Progesterone (8 mg/kg, i.v.) or its vehicle, were administered at 20 min, 2, 6, and 24h after the end of ischemia. At histological examination, brains of the ischemic vehicle-treated rats showed a severe reduction of the population of pyramidal neurons in the CA1 and CA2 subfields (12% and 29% remaining neurons, respectively), and a less severe neuronal loss in the CA3 and CA4 subfields of the hippocampus (68% and 63% remaining neurons, respectively), as compared to rats exposed to sham procedures. They also showed a two-fold enlargement of the lateral ventricles and 33% shrinkage of the cerebral cortex as compared to the sham group. Progesterone treatment resulted in a significant preservation of pyramidal neurons in CA1 and CA2 (40% and 62% remaining neurons), with no ventricular dilation and only a mild (12%) cortical shrinkage. Results suggest that progesterone is able to interfere with some late pathophysiological mechanisms leading both to selective neuronal damage in the hippocampal CA1 and CA2 subfields, and to shrinkage of the cerebral cortex.
Moralí
Gabriela
G
Unidad de Investigación Médica en Farmacología, CMN Siglo XXI, IMSS, Eugenia 626-Girasol-302, Col. Del Valle, México 03100, DF, Mexico. gmorali@hotmail.com
Letechipía-Vallejo
Graciela
G
López-Loeza
Elisa
E
Montes
Pedro
P
Hernández-Morales
Lucía
L
Cervantes
Miguel
M
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011374:Progesterone / Q000627:therapeutic use*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D011374:Progesterone