Albumin ameliorates tissue plasminogen activator-mediated blood-brain barrier permeability and ischemic brain injury in rats.
OBJECTIVE
Tissue plasminogen activator (tPA) may aggravate ischemic neuronal damage after focal cerebral ischemia and increase blood-brain barrier permeability. Human serum albumin has neuroprotective effects on ischemic stroke. However, whether albumin can attenuate the deleterious effects of tPA is yet unknown.


METHODS
In the present study, we attempted to determine the effects of albumin on cerebral injury and blood-brain barrier disruption induced by middle cerebral artery occlusion for 2 hours followed by 24 hours of reperfusion and tPA.


RESULTS
We found that infarct volume in rats which received saline and tPA was 35.6 +/- 3.8% (mean +/- SEM) and 50.9 +/- 4.5%, respectively. There was significant difference between the two groups (p<0.01). The infarct volume in rats that received tPA with albumin was significantly decreased to 29.2 +/- 3.3% (p<0.05), compared with tPA-only-treated group. Combination therapy using tPA with albumin also improved neurological deficits and reduced brain edema significantly (p<0.05). Relative to tPA-treated group, rats that received combination therapy using tPA with albumin had significantly reduced blood-brain barrier permeability, evaluated by quantitation of Evans blue leakage (p<0.05).


CONCLUSIONS
In acute ischemic stroke, combination therapy using tPA with albumin can attenuate the deleterious effects of tPA.
Tang
Jin
J
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Li
Ya-Jun
YJ
Mu
Jun
J
Li
Qi
Q
Yang
De-Yu
DY
Xie
Peng
P
D000418:Albumins / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D002199:Capillary Permeability / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000494:pharmacology; D020287:In Situ Nick-End Labeling / Q000295:instrumentation; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy*; D013778:Tetrazolium Salts; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000494:pharmacology
D000418:Albumins; D005343:Fibrinolytic Agents; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D010959:Tissue Plasminogen Activator