title: Preclinical efficacy of human Albumin in subarachnoid hemorrhage.
abstract: Human Albumin is a unique pleiotropic protein with multiple properties. Previous clinical and laboratory studies have indicated a possible beneficial effect of Albumin in subarachnoid hemorrhage (SAH). The present study aimed to further define the preclinical characteristics of Albumin. SAH was induced by endovascular perforation in Sprague-Dawley rats. In the dose-escalation study, Albumin ranging from 0.02g/kg to 1.0g/kg was intravenously infused immediately after SAH. In the therapeutic window study, 1.0g/kg Albumin was administered at 0h, 2h, 4h or 8h after SAH. Physiologic variables were monitored in different Albumin treatment regimens. One day after SAH, neurological scores, SAH scores, blood-brain barrier permeability, neural degeneration and apoptosis were examined. The efficacy of Albumin for SAH was also determined in female rats and in spontaneously hypertensive rats. We found that 0.2g/kg and 1.0g/kg Albumin significantly attenuated sensorimotor deficits, brain edema, IgG leakage, and neuronal degeneration after SAH. The benefits of Albumin existed even when the administration was delayed to 4h after SAH onset. No significant difference was found between 0.2g/kg and 1.0g/kg Albumin groups. In female rats and spontaneously hypertensive rats, Albumin likewise improved neurological outcomes and early brain injury. In conclusion, Albumin could reduce both cerebral lesions and functional deficits in the early stage of SAH. The beneficial regimen occurs within a favorable therapeutic window and is reproducible in different high-risk subjects.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; Department of Neurology, Xianlin Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Liumin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Maanshan People's Hospital, Maanshan, China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. Electronic address: yeruid@gmail.com.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Ye
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. Electronic address: xfliu2@vip.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000418:Albumins; D002317:Cardiovascular Agents; D018696:Neuroprotective Agents
keywords: behavior; blood–brain barrier; human albumin; neurovascular dysfunction; subarachnoid hemorrhage