We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery.
Background In preclinical stroke models, improvement in motor performance is associated with reorganization of cortical motor maps. However, the temporal relationship between performance gains and map plasticity is not clear. Objective This study was designed to assess the effects of rehabilitative training on the temporal dynamics of behavioral and neurophysiological endpoints in a rat model of focal cortical infarct. Methods Eight days after an ischemic infarct in primary motor cortex, adult rats received either rehabilitative training or were allowed to recover spontaneously. Motor performance and movement quality of the paretic forelimb was assessed on a skilled reach task. Intracortical microstimulation mapping procedures were conducted to assess the topography of spared forelimb representations either at the end of training (post-lesion day 18) or at the end of a three week follow-up period (post-lesion day 38). Results Rats receiving rehabilitative training demonstrated more rapid improvement in motor performance and movement quality during the training period that persisted through the follow-up period. Motor maps in both groups were unusually small on post-lesion day 18. On post-lesion day 38, forelimb motor maps in the rehabilitative training group were significantly enlarged compared with the no-rehab group, and within the range of normal maps. Conclusions Post-infarct rehabilitative training rapidly improves motor performance and movement quality after an ischemic infarct in motor cortex. However, training-induced motor improvements are not reflected in spared motor maps until substantially later, suggesting that early motor training after stroke can help shape the evolving post-stroke neural network.
Neuropathic pain is often chronic and can persist after overt tissue damage heals, suggesting that its underlying mechanism involves the alteration of neuronal function. Such an alteration can be a direct consequence of nerve damage or a result of neuroplasticity secondary to the damage to tissues or to neurons. Recent studies have shown that neuroplasticity is linked to causing neuropathic pain in response to nerve damage, which may occur adjacent to or remotely from the site of injury. Furthermore, studies have revealed that neuroplasticity relevant to chronic pain is modulated by microglia, resident immune cells of the central nervous system (CNS). Microglia may directly contribute to synaptic remodeling and altering pain circuits, or indirectly contribute to neuroplasticity through property changes, including the secretion of growth factors. We herein highlight the mechanisms underlying neuroplasticity that occur in the somatosensory circuit of the spinal dorsal horn, thalamus, and cortex associated with chronic pain following injury to the peripheral nervous system (PNS) or CNS. We also discuss the dynamic functions of microglia in shaping neuroplasticity related to chronic pain. We suggest further understanding of post-injury ectopic plasticity in the somatosensory circuits may shed light on the differential mechanisms underlying nociceptive, neuropathic, and nociplastic-type pain. While one of the prominent roles played by microglia appears to be the modulation of post-injury neuroplasticity. Therefore, future molecular- or genetics-based studies that address microglia-mediated post-injury neuroplasticity may contribute to the development of novel therapies for chronic pain.
Background During recovery from a unilateral cortical stroke, spared cortical motor areas in the contralateral (intact) cerebral cortex are recruited. Pre-clinical studies have demonstrated that compensation with the less-impaired limb may have a detrimental inhibitory effect on the intact cortical hemisphere and could impede recovery of the more-impaired limb. However, evidence from detailed neurophysiological mapping studies in animal models is lacking. Objectives The present study examines neurophysiological changes in the intact hemisphere of the rat following a unilateral ischemic infarct to cortical forelimb motor areas. Methods Eight rats were trained for two weeks on a reach and retrieval task prior to an ischemic infarct induced by the vasoconstrictor, endothelin-1 injected into the cortical grey matter encompassing the two forelimb motor representations, the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Animals were randomly assigned to an Infarct/Training group (n=4) or an Infarct/No Training group (i.e., spontaneous recovery, n=4). After a five-week post-infarct period, motor areas of the intact hemisphere (CFA and RFA) were characterized using intracortical microstimulation techniques. The resulting maps of evoked movements were compared to maps derived from CFA and RFA in normal rats (Normal, n=5; Normal/Training, n=4). Results Compared with the Normal/No Training group, CFA representations were significantly smaller in the Infarct/Training group but not in the Infarct/No Training group. No significant differences were found in RFA. Conclusions Repetitive training of the more-impaired forelimb during the post-infarct recovery period reduces the size of motor representations in the intact hemisphere.
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