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Published Online
on March 23, 2006

Stroke. 2006
Published online before print March 23, 2006, doi: 10.1161/01.STR.0000217305.82123.d8
A more recent version of this article appeared on May 1, 2006
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Submitted on September 9, 2005
Revised on November 29, 2005
Accepted on January 20, 2006

Electrical Forepaw Stimulation During Reversible Forebrain Ischemia Decreases Infarct Volume

Mark G. Burnett MD; Tomokazu Shimazu MD; Tamas Szabados PhD; Hiromi Muramatsu PhD; John A. Detre MD; and Joel H. Greenberg PhD*

From the Departments of Neurosurgery (M.G.B., H.M.) and Neurology (T. Shimazu, T. Szabados, J.A.D., J.H.G.), University of Pennsylvania School of Medicine, Philadelphia, Pa.

* To whom correspondence should be addressed. E-mail: joel{at}mail.med.upenn.edu.

Background and Purpose--Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia.

Methods--Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately.

Results--The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core.

Conclusions--Functional stimulation of ischemic tissue may decrease tissue damage and improve outcome from stroke. Although the precise mechanism of this effect remains to be determined, functional stimulation could readily be translated to clinical practice.


Key words: cerebral ischemia, focal • electrical stimulation therapy • middle cerebral artery occlusion




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T. Baba, M. Kameda, T. Yasuhara, T. Morimoto, A. Kondo, T. Shingo, N. Tajiri, F. Wang, Y. Miyoshi, C. V. Borlongan, et al.
Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway
Stroke, November 1, 2009; 40(11): e598 - e605.
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