Effects of microplasmin on recovery in a rat embolic stroke model.
OBJECTIVE
The purpose of the present study was to examine the effects of microplasmin on behavioral performance and infarct volume after middle cerebral artery occlusion (MCAO) in rats. Some experiments support that microplasmin may have neuroprotective and thrombolytic properties.


METHODS
Eighty rats underwent surgery and were embolized in the right carotid territory with a fibrin-rich embolus and randomly assigned into three groups: 5 mg/kg microplasmin, 10 mg/kg microplasmin or saline (control). Groups treated with microplasmin received 50% bolus injection 10 minutes after embolization and 50% continuous infusion during the following hour. Animals from all groups were trained to obtain high baseline scores in Montoya's staircase test before embolization and were retested during 7-14 days after surgery.


RESULTS
When pre-maturely dead animals were excluded, no differences were observed among groups regarding infarct volumes. Furthermore, mortality was significantly lower in Group 1 than in Group 2 (p<0.05) and when performances were evaluated 7-14 days after surgery, Group 1 was significantly better than Group 2 concerning fine motor performance (p<0.05) and also achieved more normal bodyweight (p<0.05).


CONCLUSIONS
Among surviving animals, 5 mg/kg microplasmin treatment had no effect compared to saline-treated control animals; 5 mg/kg microplasmin reduced mortality and improved both behavioral rehabilitation and bodyweight compared to 10 mg/kg microplasmin treatment, while saline-treated animals did not differ from animals treated with 10 mg/kg microplasmin. Overall, these results indicate a potential beneficial effect of 5 mg/kg microplasmin treatment, while 10 mg/kg may worsen outcomes.
Rasmussen
Rune Skovgaard
RS
Copenhagen Experimental Stroke Unit, Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen North, Denmark. rsr@nepa.ku.dk
Overgaard
Karsten
K
Pakola
Steve
S
Boysen
Gudrun
G
D000792:Angiography / Q000379:methods; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005341:Fibrinolysin / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009460:Neurologic Examination; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D018709:Statistics, Nonparametric; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C054561:microplasmin; D005341:Fibrinolysin