title: Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.
abstract: BACKGROUND
  The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia.
  
  
  RESULTS
  In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments.
  
  
  CONCLUSIONS
  Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi 710032, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Dong
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.forename: Zongping
authors.initials: Z
authors.lastname: Fang
authors.forename: Haidong
authors.initials: H
authors.lastname: Wei
authors.forename: Fangyun
authors.initials: F
authors.lastname: Zhu
authors.forename: Guochao
authors.initials: G
authors.lastname: Li
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006466:Hemopexin / Q000378:metabolism / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009460:Neurologic Examination; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D006466:Hemopexin; D010751:Phosphopyruvate Hydratase