Article type: Research Article
Authors: Moralí, Gabriela | Montes, Pedro | Hernández-Morales, Lucía | Monfil, Tomás | Espinosa-García, Claudia | Cervantes, Miguel
Affiliations: Unidad de Investigación Médica en
Farmacología, Centro Médico Nacional Siglo XXI, IMSS,
México DF, México | Laboratorio de Neurociencias, División de
Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas
"Dr. Ignacio Chávez", Universidad Michoacana de San Nicolás de
Hidalgo, Morelia, Michoacán, México
Note: [] Corresponding author: Gabriela Moralí, Ph.D., Unidad de
Investigación Médica en Farmacología, Centro Médico
Nacional Siglo XXI, IMSS, Eugenia 626-Girasol-302, Col. Del Valle México
03100 DF, Mexico. Tel.: +52 555 687 8606; Fax: +52 555 761 0952; E-mail:
[email protected]
Abstract: Purpose: To assess the long-term neuroprotective effects of
progesterone (P_{4}) and allopregnanolone (ALLO) on
functional and morphological parameters of the integrity of the hippocampus,
after global cerebral ischemia. Methods: Adult male Sprague-Dawley rats were subjected to a
transient severe (20 min) forebrain ischemia (Isch) episode and treated with
P_4 or ALLO (8 mg/kg i.v.) or its vehicle, at 20 min, 2,
6, 24, 48 and 72 h after ischemia. Rats subjected to Sham procedures, and
intact rats were included as non-ischemic controls. Three months after
ischemia, both the functional (spatial learning and memory, and reference and
working memory), and the morphological integrity (dimensions of the hippocampal
formation, thickness of the CA1 subfield, and pyramidal neuron population) of
the hippocampus and the medial prefrontal cortex (mPFC) were determined. Results: Treatment with P_4 or ALLO
significantly reduced the impairment in spatial learning and memory, as well as
in reference and working memory, and prevented the narrowing of the
hippocampus, otherwise induced by ischemia. This better performance of
P_4- and ALLO-treated rats than vehicle (Veh) -treated
rats, occurred in spite of a loss of pyramidal neurons in the CA1, CA2, CA3 and
hilus subfields of the Ammon's horn (remaining neurons: Isch+Veh: 21.0, 35.6,
44.1, and 40.3%; Isch+P_4: 19.9, 32.2, 41.1, and 32.5%;
Isch+ALLO: 25.5, 62.0, 73.7, and 56.7%), and non-significant changes in the
mPFC, as compared to the Intact group (100%). Conclusions: Performance of P_4- or
ALLO-treated rats in learning and memory tests suggests that these steroids
promoted neural conditions accounting for adequate functioning long after
ischemia, in spite of the loss of hippocampal pyramidal neurons.
Keywords: Neuroprotection, global cerebral ischemia, progesterone, allopregnanolone, long-term cognitive performance, hippocampal pyramidal neurons loss
DOI: 10.3233/RNN-2011-0571
Journal: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 1-15, 2011
Received 9 February 2011
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Accepted 9 February 2011
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Published: 2011
