Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice

Chao Jiang, Fangfang Zuo, Yuejuan Wang, Jieru Wan, Zeng Jin Yang, Hong Lu, Wenwu Chen, Weidong Zang, Qingwu Yang, Jian Wang

Research output: Contribution to journalArticle

Abstract

In this study, we examined the effect of progesterone on histopathologic and functional outcomes of intracerebral hemorrhage (ICH) in 10- to 12-month-old mice. Progesterone or vehicle was administered by intraperitoneal injection 1 hour after collagenase-induced ICH and then by subcutaneous injections at 6, 24, and 48 hours. Oxidative and nitrosative stress were assayed at 12 hours post-ICH. Injury markers were examined on day 1, and lesion was examined on day 3. Neurologic deficits were examined for 28 days. Progesterone posttreatment reduced lesion volume, brain swelling, edema, and cell degeneration and improved long-term neurologic function. These protective effects were associated with reductions in protein carbonyl formation, protein nitrosylation, and matrix metalloproteinase-9 activity and attenuated cellular and molecular inflammatory responses. Progesterone also reduced vascular endothelial growth factor expression, increased neuronal-specific Na+/K+ ATPase a3 subunit expression, and reduced protein kinase C-dependent Na+/K+ ATPase phosphorylation. Furthermore, progesterone reduced glial scar thickness, myelin loss, brain atrophy, and residual injury volume on day 28 after ICH. With multiple brain targets, progesterone warrants further investigation for its potential use in ICH therapy.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalNeurobiology of Aging
Volume42
DOIs
StatePublished - Jun 1 2016

Keywords

  • Inflammatory response
  • Intracerebral hemorrhage
  • Neurologic function
  • Neuroprotective effects
  • Progesterone

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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