Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat.
OBJECTIVE
Acute intracerebral hemorrhage (ICH) is a common and severe form of stroke. To date, medical management of ICH has had scant impact on morbidity and mortality. Because albumin therapy is markedly neuroprotective in preclinical models of ischemic stroke, and because ischemic and hemorrhagic stroke share several common injury mechanisms, we hypothesized that albumin therapy might also benefit ICH.


METHODS
Acute intracortical hematoma was produced in anesthetized, normothermic rats by the single stereotaxic injection of 50 muL of autologous, nonheparinized whole blood over 5 minutes. Separate animal groups were treated either with 25% human albumin, 1.25 g/kg, or with intravenous saline vehicle at 60 minutes after ICH. Neurobehavior was quantified sequentially over the next 2 to 7 days. Damage to the blood-brain barrier was assessed at 2 days after ICH by fluorometric measurement of Evans blue extravasation in dissected brain regions.


RESULTS
High-grade neurological deficits were present in all rats at 50 minutes after ICH (score 10.3+/-0.2, mean+/-SEM [maximal score 12]). Albumin-treated rats showed improved neuroscores relative to saline-treated animals beginning within hours of treatment and persisting throughout the 7-day survival period. At 3 and 7 days, mean total neuroscores of the albumin group were 38% to 43% lower than in saline-treated animals. Perihematomal Evans blue discoloration was readily evident in saline-treated ICH rats but was reduced by albumin treatment. Hemispheric Evans blue content ipsilateral to the hematoma was reduced by 49% by albumin treatment (albumin 93.9+/-13.3 versus saline 184.7+/-33.7 mg/g, P<0.05). Hematoma volume and brain swelling were not affected by albumin treatment.


CONCLUSIONS
Prompt albumin therapy improves neurological function and blood-brain barrier integrity after acute intracortical hematoma. These observations have important potential clinical implications.
Belayev
Ludmila
L
Cerebral Vascular Disease Research Center, Department of Neurology (D4-5), University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USA. lbelayev@stroke.med.miami.edu
Saul
Isabel
I
Busto
Raul
R
Danielyan
Kristine
K
Vigdorchik
Alexey
A
Khoutorova
Larissa
L
Ginsberg
Myron D
MD
D000418:Albumins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000628:therapy; D005070:Evans Blue / Q000494:pharmacology; D005470:Fluorometry; D006406:Hematoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D000418:Albumins; D018696:Neuroprotective Agents; D012965:Sodium Chloride; D005070:Evans Blue