Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage.

Abstract

BACKGROUND:

Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH.

METHODS:

We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically.

RESULTS:

PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days.

CONCLUSIONS:

PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH.

• Authors: Nefize Turan, Brandon A Miller, J Russell Huie, Robert A Heider, Jun Wang, Bushra Wali, Seema Yousuf, Adam R Ferguson, Iqbal Sayeed, Donald G Stein, Gustavo Pradilla
• Journal: World neurosurgery (World Neurosurg) Vol. 110 Pg. e150-e159 (Feb 2018) ISSN: 1878-8769 [Electronic] United States
• PMID: 29097330 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Neuroprotective Agents
• Receptors, AMPA
• Synaptophysin
• Progesterone
• glutamate receptor ionotropic, AMPA 1

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Basilar Artery (drug effects, immunology, pathology)
• Brain (drug effects, pathology, physiopathology)
• Cell Proliferation (drug effects, physiology)
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Microglia (drug effects, pathology, physiology)
• Motor Activity (drug effects, physiology)
• Muscle Strength (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Progesterone (pharmacology)
• Random Allocation
• Receptors, AMPA (metabolism)
• Recovery of Function (drug effects, physiology)
• Subarachnoid Hemorrhage (drug therapy, pathology, physiopathology)
• Synaptophysin (metabolism)
• Vasospasm, Intracranial (drug therapy, pathology, physiopathology)