title: Human Albumin Improves Long-Term Behavioral Sequelae After Subarachnoid Hemorrhage Through Neurovascular Remodeling.
abstract: OBJECTIVE
  Subarachnoid hemorrhage results in significant long-lasting neurologic sequelae. Here, we investigated whether human albumin improves long-term outcomes in experimental subarachnoid hemorrhage and whether neurovascular remodeling is involved in the protection of albumin.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  Hospital research laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Rats underwent subarachnoid hemorrhage by endovascular perforation. Albumin of either 0.63 or 1.25 g/kg was injected IV immediately after the surgery. Modified Garcia test, beam-walking test, novel object recognition, and Morris water maze were employed to determine the behavioral deficits. The effects of albumin on early neurovascular dysfunction and chronic synaptic plasticity were also studied.
  
  
  RESULTS
  Both doses of albumin significantly improved the sensorimotor scores (F = 31.277; p = 0.001) and cognitive performance (F = 7.982; p = 0.001 in novel object recognition test; and F = 3.431; p = 0.026 in the latency analysis of Morris water maze test) for at least 40 days after subarachnoid hemorrhage. There were remarkable microvasculature hypoperfusion, intracranial pressure rise, early vasoconstriction, neural apoptosis, and degeneration in subarachnoid hemorrhage rats, with albumin significantly attenuating such neurovascular dysfunction. Furthermore, albumin markedly prevented blood-brain barrier disruption, as indicated by less blood-brain barrier leakage, preserved blood-brain barrier-related proteins, and dampened gelatinase activities. The expressions of key synaptic elements were up-regulated with albumin supplementation in both acute and chronic phases. Accordingly, a higher dendritic spine density was observed in the prefrontal and hippocampal areas of albumin-treated subarachnoid hemorrhage animals.
  
  
  CONCLUSIONS
  Albumin at low-to-moderate doses markedly improves long-term neurobehavioral sequelae after subarachnoid hemorrhage, which may involve an integrated process of neurovascular remodeling.
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaohao
authors.initials: X
authors.lastname: Zhang
authors.forename: Liumin
authors.initials: L
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xiong
authors.forename: Lian
authors.initials: L
authors.lastname: Yang
authors.forename: Hongfei
authors.initials: H
authors.lastname: Sang
authors.forename: Ruidong
authors.initials: R
authors.lastname: Ye
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000209:etiology*; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology*; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D066253:Vascular Remodeling
chemical_list: D000418:Albumins