Nitric oxide may contribute to the long-term impairment of synaptic transmission after transient ischemia.

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 …