http://www.neurology.org/content/86/16_Supplement/P5.224.short
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April 5, 2016 vol. 86 no. 16 Supplement P5.224Neurology
- Abstract
Abstract
Objective:
To determine the effect of rehabilitation on
oligodendrocyte progenitor cell (OPC) activity and neural repair in a
mouse model
of white matter stroke (WMS).
Background:
Physical activity has profound effects on white
matter function. In humans, exercise mitigates the effect of progressive
WMS
on gait. Moreover, constraint-induced repeated use
of the affected arm in both stroke patients and animal models enhances
recovery. OPCs, which can mature into myelinating
oligodendrocytes, are potential mediators of white matter repair. OPC
proliferation
and myelination in rodent cortex are promoted by
neuronal activity and environmental stimulation. However, the effects of
a specific motor task (like those performed by
post-stroke patients in rehabilitation) in WMS have not yet been
studied. Here
we evaluated the effect of a skilled reach task on
OPC activity in WMS.
Methods:
Three- and 20-month-old mice were trained on a
skilled reach task for three weeks. WMS was then induced in the
subcortical
white matter underlying the motor cortex
contralateral to the trained limb via injection of a vasoconstrictor.
Mice were then
divided into two groups: three weeks of continued
reach task (to model the skilled limb use employed in human
neurorehabilitation),
or no reach task. Functional recovery of the mice
was quantified with a skilled forelimb eating task. Brain tissues were
analyzed
using immunohistochemistry.
Results:
Relative to mice receiving no post-stroke
rehabilitation, the skilled reach mice show greater numbers of OPCs in
subcortical
white matter. The effect is more pronounced for
3-month-old mice compared to 20-month-old mice. Lineage tracing via
immunohistochemistry
suggests OPCs in the skilled reach group have
increased potential to develop into mature oligodendrocytes.
Conclusions:
Rehabilitation with skilled reach after WMS in this
mouse model potentiates two critical components of white matter repair:
the number of OPCs, as well as their ability to
mature.
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