title: Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice.
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 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.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Henan, People's Republic of China; Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address: chaojzzu@126.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Henan, People's Republic of China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zuo
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Henan, People's Republic of China.
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Jieru
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Zengjin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zang
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address: jwang79@jhmi.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001284:Atrophy; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage* / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066127:White Matter / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone; D020780:Matrix Metalloproteinase 9; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Inflammatory response; Intracerebral hemorrhage; Neurologic function; Neuroprotective effects; Progesterone