Editors' ChoiceNeurological Disease

Shining a Light on Stroke

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Science Translational Medicine  16 Feb 2011:
Vol. 3, Issue 70, pp. 70ec21
DOI: 10.1126/scitranslmed.3002210

Stroke remains a common and serious consequence of numerous underlying illnesses and risk factors, such as hypertension and diabetes. Understanding how the brain changes after stroke may help to advance treatments for this illness. To this end, Barth and Mody have developed an improved in vivo model of the anatomy and physiology of ischemic stroke that uses photothrombosis—occlusion of a blood vessel through injection of a dye followed by irradiation—combined with stereotaxic localization (the use of a three-dimensional coordinate system to place the optic fiber) to monitor neurological changes before and after ischemic stroke.

The researchers inserted the optic fiber into the hippocampal artery of mice to isolate blood flow to the hippocampus, a brain region that is important in learning and memory and is particularly vulnerable to ischemic stroke. Blood flow was then selectively blocked in the artery through light activation of a photosensitive dye, rose bengal, which induced blood clot formation. Measuring neuron population activity in the hippocampus before and after this procedure, the authors observed a massive, brief high-frequency epileptiform discharge (HFD) in affected neurons, followed by a negative shift in the baseline electrical potential, which is consistent with neuronal depolarization due to hypoxia (inadequate oxygen). This was followed by a long-lasting decrease in neuron oscillatory activity in the gamma range (30 to 119 Hz), which is generally important to complex cognitive processes such as memory. Interestingly, only the initial HFD was also observed in the contralateral hippocampus, which is often affected by the spread of seizure activity from the other side of the brain.

This work elegantly characterizes the neurophysiological changes that unfold in the wake of stroke, thus setting the stage for elaboration of the biochemical basis and time course of these changes. These findings also suggest that events, such as the HFD and subsequent negative electrical potential, might provide specific targets for therapeutic intervention aimed at attenuating epileptiform activity or other disturbances in electrical activity, ultimately to mitigate the deleterious effects of these processes on the brain. Such knowledge should aid in the development of new therapies designed to restore brain function in stroke survivors.

A. M. I. Barth, I. Mody, Changes in hippocampal neuronal activity during and after unilateral selective hippocampal ischemia in vivo. J. Neurosci. 31, 851–860 (2011). [Abstract]

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