Neuroprotective effect of treatment with human albumin in permanent focal cerebral ischemia: histopathology and cortical perfusion studies.
In recent experimental studies, we demonstrated a highly beneficial neuroprotective effect of moderate- to high-dose human albumin treatment of transient focal cerebral ischemia, but we did not define the effect of albumin therapy in permanent focal cerebral ischemia. In this study, anesthetized Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion by retrograde insertion of an intraluminal nylon suture coated with poly-L-lysine. Albumin was administered i.v. at 2 h after onset of middle cerebral artery occlusion, in doses of either 1.25 (n=8) or 2.5 g/kg (n=6). In a separate group of animals, albumin (2.5 g/kg) was given 1 h after middle cerebral artery occlusion (n=6). Vehicle-treated rats (n=6) received 0.9% saline in equivalent volumes. Neurological status was evaluated during and 24 h after middle cerebral artery occlusion. One day after middle cerebral artery occlusion, infarct volumes and brain edema were determined. In a separate group of animals, cortical perfusion was assessed by Laser-Doppler perfusion imaging. Albumin (1.25 g/kg; n=3) or vehicle (sodium chloride 0.9%; n=3) was administered at 2 h after onset of middle cerebral artery occlusion. Higher-dose albumin therapy (2.5 g/kg) significantly improved the neurological score compared to vehicle rats at 24 h, when administered at either 1 or 2 h after middle cerebral artery occlusion. Total infarct volume was reduced by albumin (2.5 g/kg given at 2 h) by 32% compared with vehicle-treated rats. Both albumin doses (1.25 and 2.5 g/kg) significantly reduced cortical and striatal infarct areas at several coronal levels when administered at 2 h after middle cerebral artery occlusion. Brain swelling was not affected by albumin treatment. Cortical perfusion declined during middle cerebral artery occlusion in both groups. Treatment with albumin led to 48% increases in cortical perfusion (P<0.002), but saline caused no change. These results support a beneficial effect of albumin therapy in permanent focal cerebral ischemia.
Liu
Y
Y
Cerebral Vascular Disease Research Center, Department of Neurology (D4-5), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.
Belayev
L
L
Zhao
W
W
Busto
R
R
Belayev
A
A
Ginsberg
M D
MD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D017078:Laser-Doppler Flowmetry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology*
D018696:Neuroprotective Agents; D012709:Serum Albumin