Diabetes impairs cortical plasticity and functional recovery following Ischemic stroke

Danielle Sweetnam, Andrew Holmes, Kelly A. Tennant, Akram Zamani, Mark Walle, Paul Jones, Charles Wong, Craig E. Brown

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54 Citations (Scopus)

Abstract

Diabetics are at greater risk of having a stroke and are less likely to recover from it. To understand this clinically relevant problem, we induced an ischemic stroke in the primary forelimb somatosensory (FLS1) cortex of diabetic mice and then examined sensory-evoked changes in cortical membrane potentials and behavioral recovery of forelimb sensory-motor function. Consistent with previous studies, focal stroke in non-diabetic mice was associated with acute deficits in forelimb sensorimotor function and a loss of forelimb evoked cortical depolarizations in peri-infarct cortex that gradually recovered over several weeks time. In addition, we discovered that damage to FLS1 cortex led to an enhancement of forelimb evoked depolarizations in secondary forelimb somatosensory (FLS2) cortex. Enhanced FLS2 cortical responses appeared to play a role in stroke recovery given that silencing this region was sufficient to reinstate forelimb impairments. By contrast, the functional reorganization of FLS1 and FLS2 cortex was largely absent in diabetic mice and could not be explained by more severe cortical infarctions. Diabetic mice also showed persistent behavioral deficits in sensorimotor function of the forepaw, which could not be rescued by chronic insulin therapy after stroke. Collectively these results indicate that diabetes has a profound effect on brain plasticity, especially when challenged, as is often the case, by an ischemic event. Further, our data suggest that secondary cortical regions play an important role in the restoration of sensorimotor function when primary cortical regions are damaged.

Original languageEnglish
Pages (from-to)5132-5143
Number of pages12
JournalJournal of Neuroscience
Volume32
Issue number15
DOIs
Publication statusPublished - 11 Apr 2012
Externally publishedYes

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