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(Stroke. 2005;36:1823.)
© 2005 American Heart Association, Inc.

Letters to the Editor

Inosine, Calcium Channels, and Neuroprotection Against Ischemic Brain Injury

Kazushi Tsuda, MD, FAHA

Division of Cardiology, Department of Medicine, Wakayama Medical University, Wakayama, Japan

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

We read with great interest the article by Shen et al,¹ dealing with neuroprotective effects of inosine against ischemic brain injury. The results of their study demonstrated that intracerebroventricular administration of inosine before middle cerebral artery occlusion in rats resulted in a higher level of locomotor activity and less cerebral infarction. In addition, they indicated that coadministration of selective A3 receptor antagonist MRS1191 significantly attenuated inosine-mediated protection. In the electrophysiological study, it was shown that inosine antagonized glutamate-induced excitation in cerebral cortical neurons. The authors proposed that inosine may inhibit glutamate postsynaptic responses and reduce cerebral infarction via the activation of A3 receptors.

Several studies have shown the mechanisms for glutamate-induced excitation of neural cells. In a study we presented earlier, changes in acetylcholine (ACh) release evoked by glutamate was investigated in rat central nervous system.^2,3 In an in vitro study, we showed that glutamate increased the release of ACh from rat striatum, which was inhibited by the N-methyl-D-aspartate type of glutamate receptor antagonist MK-801.³ Furthermore, it was demonstrated that the calcium-channel blocker verapamil significantly reduced glutamate-evoked ACh release and that the inhibitory effect was more pronounced in the presence of magnesium.² It might be possible that the calcium-channel blocker could inhibit the N-methyl-D-aspartate receptor–dependent calcium current in neural cells. It was also shown that the calcium-channel blocker nilvadipine blocked glutamate-evoked intracellular calcium increase with a concomitant reduction in glutamate-induced apoptosis in purified retinal ganglion cells,⁴ suggesting that the calcium-channel blocker . . . [Full Text of this Article]

Hui Shen, MD; Guann-Juh Chen, MD; Brandon Harvey, PhD Yun Wang, MD, PhD

Neural Protection and Regeneration Section, National Institute on Drug Abuse, Baltimore, Md