Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.
There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures.
['Peterson|Bethany L|BL|', 'Won|Soonmi|S|', 'Geddes|Rastafa I|RI|', 'Sayeed|Iqbal|I|', 'Stein|Donald G|DG|']
D000818:Animals D000831:Animals, Newborn D001921:Brain D002340:Carotid Artery Diseases D017536:Carotid Artery, Common D003072:Cognition Disorders D004195:Disease Models, Animal D005260:Female D020925:Hypoxia-Ischemia, Brain D008297:Male D018782:Maze Learning D017628:Microglia D009043:Motor Activity D018696:Neuroprotective Agents D011374:Progesterone D011897:Random Allocation D017207:Rats, Sprague-Dawley D012018:Reflex D012727:Sex Characteristics D016896:Treatment Outcome
Sex difference Microglia Neuroplasticity CNS repair Cell proliferation Development