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

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• 作者：Chao Jiang^a ; ^b ; ^{chaojzzu@126.com" class="auth_mail" title="E-mail the corresponding author} ; Fangfang Zuo^a ; Yuejuan Wang^a ; Jieru Wan^b ; Zengjin Yang^b ; Hong Lu^c ; Wenwu Chen^b ; Weidong Zang^b ; Qingwu Yang^d ; Jian Wang^b ; ^{jwang79@jhmi.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Progesterone ; Neuroprotective effects ; Inflammatory response ; Neurologic function ; Intracerebral hemorrhage
• 刊名：Neurobiology of Aging
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：42
• 期：Complete
• 页码：13-24
• 全文大小：3554 K

文摘

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 ɑ3 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.