Published Online
on November 3, 2005

A more recent version of this article appeared on December 1, 2005

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Submitted on May 19, 2005
Revised on August 8, 2005
Accepted on September 23, 2005

A Model of Mini-Embolic Stroke Offers Measurements of the Neurovascular Unit Response in the Living Mouse

Zheng Gang Zhang MD, PhD^*; Li Zhang MD; Guangliang Ding PhD; Quan Jiang PhD; Rui Lan Zhang MD; Xueguo Zhang MD; Wen-Biao Gan PhD; and Michael Chopp PhD

From the Department of Neurology (Z.G.Z., L.Z., G.D., Q.J., R.L.Z., X.Z., M.C.), Henry Ford Health Sciences Center, Detroit, Mich; Department of Physics (M.C.), Oakland University, Rochester, Mich; Molecular Neurobiology Program (W.-B.G.), Skirball Institute, and Department of Neuroscience and Physiology, New York University School of Medicine, New York.

^* To whom correspondence should be addressed. E-mail: zhazh{at}neuro.hfh.edu.

Background and Purpose--To measure cerebral vascular and neuronal responses after stroke in the living mouse, we generated a mouse model of embolic stroke localized to the parietal cortex.

Methods--Male C57/6J or male transgenic mice (2 to 3 months old) expressing yellow fluorescent protein (YFP) were used in the present study. A single fibrin-rich clot (8 mm in length) was injected into a branch of the right middle cerebral artery (MCA). MRI measurements were performed to measure ischemic lesion. Using confocal and 2-photon microscopy, changes in the embolus, dendrites, and dendritic spines were measured in the living mouse.

Results--Eight of 11 mice (73%) had the embolus localized to a branch of the right MCA in the parietal cortex. Expansion of the embolus within the artery was observed 24 hours after stroke. The presence of ischemic lesion in the parietal cortex was verified by MRI measurements, and histopathological analysis revealed that these mice (n=8) had a cortical infarct volume of 4.9±3.6% of the contralateral hemisphere. In the living mouse, substantial loss of YFP-labeled axonal and dendritic structures as well as the formation of abnormal dendritic bulbs were detected in the ischemic boundary regions 24 hours after stroke compared with that 1 hour after stroke.

Conclusion--This model offers a novel approach to study the neurovascular unit in cerebral cortex after stroke in the living mouse.

Key words: cerebral ischemia • image • mice

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