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(Stroke. 2002;33:2348.)
© 2002 American Heart Association, Inc.

Letters to the Editor

Nitric Oxide May Contribute to the Long-Term Impairment of Synaptic Transmission After Transient Ischemia

A.A. Mongin, PhD

Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York

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

To the Editor:

In their appealing study published in a recent issue of Stroke, Bolay et al¹ extend their previous observations² that relatively mild ischemia causes long-term dysfunction of synaptic transmission and now suggest that a likely mechanism for this phenomenon is persistent inhibition of presynaptic signaling and neurotransmitter release. In their convincing experiments, the authors demonstrate that 1-hour middle cerebral artery occlusion causes selective inhibition of synapsin-I phosphorylation in the ischemic penumbra of the rat cortex and propose this as a key reason for the suppression of vesicular neurotransmitter release. Interestingly, the postsynaptic elements of neuronal networks seem to remain intact and continue to respond to exogenously applied glutamate. These findings, together with previous data on ischemia-induced inactivation of Ca²⁺/calmodulin-dependent protein kinase II³ and protein kinase A,⁴ create a new picture of how relatively mild ischemia or transient ischemic attack may cause long-term impairment of brain function despite survival of neuronal cells.

I agree with the authors that phosphorylation defects likely contribute to the long-lasting suppression of synaptic transmission. However, I would like to attract the attention of the authors and readers to an additional possible mechanism of synaptic transmission impairment. It is a well-known fact that ischemia upregulates production of the free radical nitric oxide (NO).⁵ In the healthy brain, NO serves as a vasorelaxant and neuromodulator. In contrast, under pathological conditions, neuronally derived NO and several related nitrogen reactive species play major roles in mediating brain damage.^5,6 One such pathological NO product, peroxynitrite (ONOO^-), is formed in . . . [Full Text of this Article]

Hayrunnisa Bolay, MD, PhD

Department of Neurology, Faculty of Medicine, Gazi University, Ankara, Turkey

Turgay Dalkara, MD, PhD

Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey