Acute enoxaparin treatment widens the therapeutic window for tPA in a mouse model of embolic stroke.

Objectives: The purpose of this experiment was to determine if the low molecular weight heparin ( LMWH) enoxaparin could extend the treatment window for thrombolysis in a mouse model of embolic stroke. Methods: To establish the treatment window, mice were treated with tPA 2, 3 or 4 hours after clot insertion. Results showed that only the 2 hour treatment group exhibited infarct volumes significantly smaller than untreated controls. We attempted to widen this window by pre-treating mice with enoxaparin ( 10 mg/kg, s.c.; n = 36) 1 hour before embolization. A control group (n = 24) was given a saline injection. The enoxaparin-treated animals were subdivided and treated with tPA either 4 ( n = 12) or 6 hours ( n = 12) after clot insertion, while the third group ( n = 12) was given saline. The saline-pre-treated mice were dived into two groups: one group ( n = 12) received tPA and the other group ( n = 12) received saline 4 hours post-stroke. Embolization was confirmed by laser Doppler flowmetry and the effects of the resulting infarcts were evaluated by triphenyltetrazolium chloride staining and by behavioral testing. Results: Results showed large infarcts and impaired sensorimotor coordination in the saline pre-treated animals confirming the narrow treatment window. Enoxaparin pre-treatment produced significantly smaller infarcts and improved motor behavior in groups treated with tPA both 4 and 6 hours after embolization. Neither the 4 nor the 6 hour tPA-treated groups showed evidence of intracerebral hemorrhage or external bleeding. Conclusion: These data indicate that the LMWH enoxaparin can significantly increase the therapeutic time window in a mouse model of embolic stroke.