Human albumin therapy of acute ischemic stroke: Marked neuroprotective efficacy at moderate doses and with a broad therapeutic window

Ludmila Belayev, Yitao Liu, Weizhao Zhao, Raul Busto, Myron Ginsberg

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Background and Purpose - We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. Methods - Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. Results - Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%). Conclusions - Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.

Original languageEnglish
Pages (from-to)553-560
Number of pages8
JournalStroke
Volume32
Issue number2
StatePublished - Feb 26 2001

Fingerprint

Albumins
Middle Cerebral Artery Infarction
Stroke
Brain Edema
Sutures
Therapeutics
Corpus Striatum
Nitrous Oxide
Halothane
Infarction
Lysine
Sprague Dawley Rats
Ischemia
Perfusion
Brain

Keywords

  • Brain edema
  • Cerebral ischemia
  • Focal
  • Hemodilution
  • Middle cerebral artery occlusion
  • Neuroprotection

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Human albumin therapy of acute ischemic stroke : Marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. / Belayev, Ludmila; Liu, Yitao; Zhao, Weizhao; Busto, Raul; Ginsberg, Myron.

In: Stroke, Vol. 32, No. 2, 26.02.2001, p. 553-560.

Research output: Contribution to journalArticle

@article{4f71e303a4ee427aafaa5c93dc53c808,
title = "Human albumin therapy of acute ischemic stroke: Marked neuroprotective efficacy at moderate doses and with a broad therapeutic window",
abstract = "Background and Purpose - We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. Methods - Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. Results - Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67{\%} and 58{\%}, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68{\%}), subcortical regions (by 52{\%}), and total infarct (by 61{\%}). Conclusions - Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.",
keywords = "Brain edema, Cerebral ischemia, Focal, Hemodilution, Middle cerebral artery occlusion, Neuroprotection",
author = "Ludmila Belayev and Yitao Liu and Weizhao Zhao and Raul Busto and Myron Ginsberg",
year = "2001",
month = "2",
day = "26",
language = "English",
volume = "32",
pages = "553--560",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Human albumin therapy of acute ischemic stroke

T2 - Marked neuroprotective efficacy at moderate doses and with a broad therapeutic window

AU - Belayev, Ludmila

AU - Liu, Yitao

AU - Zhao, Weizhao

AU - Busto, Raul

AU - Ginsberg, Myron

PY - 2001/2/26

Y1 - 2001/2/26

N2 - Background and Purpose - We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. Methods - Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. Results - Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%). Conclusions - Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.

AB - Background and Purpose - We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. Methods - Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. Results - Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%). Conclusions - Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.

KW - Brain edema

KW - Cerebral ischemia

KW - Focal

KW - Hemodilution

KW - Middle cerebral artery occlusion

KW - Neuroprotection

UR - http://www.scopus.com/inward/record.url?scp=0035133027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035133027&partnerID=8YFLogxK

M3 - Article

C2 - 11157196

AN - SCOPUS:0035133027

VL - 32

SP - 553

EP - 560

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 2

ER -