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Stroke. 2014 Feb;45(2):619-22. doi: 10.1161/STROKEAHA.113.003823. Epub 2013 Dec 24.

Effects of tissue plasminogen activator and annexin A2 combination therapy on long-term neurological outcomes of rat focal embolic stroke.

Author information

1
From the Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Xiaoshu Wang, Z.L.); and Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA (Xiaoshu Wang, X.F., Z.Y., Z.L., J.Z., E.M., S.G., E.H.L., Xiaoying Wang).

Abstract

BACKGROUND AND PURPOSE:

Tissue-type plasminogen activator (tPA) in combination with recombinant annexin A2 (rA2) is known to reduce acute brain damage after focal ischemia. Here, we ask whether tPA-plus-rA2 combination therapy can lead to sustained long-term neurological improvements as well.

METHODS:

We compared the effects of intravenous high-dose tPA alone (10 mg/kg) versus a combination of low-dose tPA (5 mg/kg) plus 10 mg/kg rA2 in a model of focal embolic cerebral ischemia in rats. All rats were treated at 3 hours after embolization. Brain tissue and neurological outcomes were assessed at 1 month. Surrogate biomarkers for endogenous neurovascular remodeling in peri-infarct area were analyzed by immunohistochemistry.

RESULTS:

Compared with high-dose tPA alone, low-dose tPA-plus-rA2 significantly decreased infarction and improved neurological function at 1-month poststroke. In peri-infarct areas, tPA-plus-rA2 combination therapy also significantly augmented microvessel density, vascular endothelial growth factor, and synaptophysin expression.

CONCLUSIONS:

Compared with conventional high-dose tPA alone, combination low-dose tPA plus rA2 therapy may provide a safe and effective way to improve long-term neurological outcomes after stroke.

KEYWORDS:

annexin A2; drug therapy, combination; rats; tissue plasminogen activator

PMID:
24368559
PMCID:
PMC3912312
DOI:
10.1161/STROKEAHA.113.003823
[Indexed for MEDLINE]
Free PMC Article
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