Application of albumin prior to delayed thrombolysis reduces brain edema and blood brain barrier permeability in an embolic stroke model.
To explore whether human albumin (Alb) administration prior to thrombolysis with recombinant tissue plasminogen activator (rt-PA) can eliminate brain damage induced by this treatment given after the effective and safe window of 3h after stroke onset. Rats were subjected to embolic stroke by unilateral embolic middle cerebral artery occlusion (MCAO). Three or six hours after the onset of stroke, rats were administered intravenously with saline (control), rt-PA (thrombolysis) or rt-PA+Alb (additional Alb 3h after MCAO, combination). Cerebral blood flow, infarct volume, space-occupying effect and blood brain barrier (BBB) leakage of gadopentetate dimeglumine (Gd-DTPA) were assessed dynamically by magnetic resonance imaging (MRI) at 24h, 7 and 14days after treatment. BBB leakage of both fluoro-isothiocyanate dextran (FITC-dextran) and erythrocytes was also evaluated 14days after treatment. The space-occupying effect in the combination group at 7days after treatment declined significantly compared with that at 24h after treatment (P<0.05), but additional Alb treatment failed to reduce the infarct volumes or improve cerebral blood volume. Furthermore, BBB leakage of both small (Gd-DTPA) and large (FITC-dextran and erythrocytes) molecules decreased significantly in the combination compared to the saline or thrombolysis groups (P<0.05). Alb administration prior to thrombolysis (3h after stroke) can reduce delayed rt-PA treatment-induced brain edema and BBB permeability.
Institute of Interventional and Diagnostic Radiology, The Sixth Affiliated People's Hospital, Shanghai Jiao Tong University, No. 600, Yi Shan Road, Shanghai 200233, China.
Hai-Tao
HT
Lu
Jun-Gong
JG
Zhao
Ming-Hua
MH
Li
Yong-Dong
YD
Li
D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001929:Brain Edema / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020766:Intracranial Embolism / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010539:Permeability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012709:Serum Albumin / Q000008:administration & dosage*; D000075462:Serum Albumin, Human; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
C422455:ALB protein, human; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D012709:Serum Albumin; D010959:Tissue Plasminogen Activator; D000075462:Serum Albumin, Human