Stroke induces pathophysiological and adaptive processes in regions proximal and distal to the
infarct. Recent studies suggest that plasticity at the level of the spinal cord may contribute to sensorimotor recovery after cortical
stroke. Here, we compare the time course of heightened structural plasticity in the spinal cord against the temporal profile of cortical plasticity and spontaneous behavioral recovery. To examine the relation between trophic and inflammatory effectors and spinal structural plasticity, spinal expression of
brain derived neurotrophic factor (
BDNF), neurotrophin-3 (NT-3),
tumor necrosis factor-α (TNF-α), and
interleukin-6 (IL-6) was measured.
Growth-associated protein 43 (GAP-43), measured at 3, 7, 14, or 28 days after photothrombotic
stroke of the forelimb sensorimotor cortex (FL-SMC) to provide an index of periods of heightened structural plasticity, varied as a function of lesion size and time after
stroke in the cortical hemispheres and the spinal cord. Notably,
GAP-43 levels in the cervical spinal cord were significantly increased after FL-SMC lesion, but the temporal window of elevated structural plasticity was more finite in spinal cord relative to ipsilesional cortical expression (returning to baseline levels by 28 post-
stroke). Peak
GAP-43 expression in spinal cord occurred during periods of accelerated spontaneous recovery, as measured on the Montoya Staircase reaching task, and returned to baseline as recovery plateaued. Interestingly, spinal
GAP-43 levels were significantly correlated with spinal levels of the inflammatory
cytokines TNF-α and
IL-6 as well as the
neurotrophin NT-3, while a transient increase in
BDNF levels preceded elevated
GAP-43 expression. These data identify a significant but time-limited window of heightened structural plasticity in the spinal cord following
stroke that correlates with spontaneous recovery and the spinal expression of inflammatory
cytokines and
neurotrophic factors.