Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

Abstract

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.

• Authors: Bethany L Peterson, Soonmi Won, Rastafa I Geddes, Iqbal Sayeed, Donald G Stein
• Journal: Behavioural brain research (Behav Brain Res) Vol. 286 Pg. 152-65 (Jun 01 2015) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 25746450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• Progesterone

Topics

• Animals
• Animals, Newborn
• Brain (drug effects, growth & development, pathology, physiopathology)
• Carotid Artery Diseases
• Carotid Artery, Common
• Cognition Disorders (drug therapy, pathology, physiopathology)
• Disease Models, Animal
• Female
• Hypoxia-Ischemia, Brain (drug therapy, pathology, physiopathology)
• Male
• Maze Learning (drug effects, physiology)
• Microglia (drug effects, pathology, physiology)
• Motor Activity (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Progesterone (metabolism, pharmacology)
• Random Allocation
• Rats, Sprague-Dawley
• Reflex (drug effects, physiology)
• Sex Characteristics
• Treatment Outcome