Enriched rehabilitative training promotes improved forelimb motor
function and enhanced dendritic growth after focal ischemic injury
The Journal of Neuroscience, 21 (14):
5272--80 (July 2001)Abstract
Chronic impairment of forelimb and digit movement is a common problem
after stroke that is resistant to therapy. Previous studies have
demonstrated that enrichment improves behavioral outcome after focal
ischemia; however, postischemic enrichment alone is not capable of
enhancing fine digit and forelimb function. Therefore, we combined
environmental enrichment with daily skilled-reach training to assess
the effect of intensive task-specific rehabilitation on long-term
functional outcome. Rats were subjected to either endothelin-1-induced
focal ischemia or sham surgery and subsequently designated to enriched-rehabilitation
or standard-housing treatment groups starting 15 d after ischemia.
Functional assessment of the affected forelimb at 4 and 9 weeks after
treatment revealed that ischemic plus enrichment (IE) animals had
improved approximately 30\% on the staircase-reaching task and were
indistinguishable from sham animals for both latency and foot faults
in a beam-traversing task. In contrast, ischemic plus standard (IS)
animals remained significantly impaired on both tasks. Interestingly,
both ischemic groups (IE and IS) relied on the nonaffected forelimb
during upright weight-bearing movements, a pattern that persisted
for the duration of the experiment. Dendritic arborization of layer
V pyramidal cells within the undamaged motor cortex was examined
using a Golgi-Cox procedure. IE animals showed enhanced dendritic
complexity and length compared with both IS and sham groups. These
results suggest that enrichment combined with task-specific rehabilitative
therapy is capable of augmenting intrinsic neuronal plasticity within
noninjured, functionally connected brain regions, as well as promoting
enhanced functional outcome.