Use-Dependent Exaggeration of Neuronal Injury after Unilateral Sensorimotor Cortex Lesions

Abstract

Unilateral injury to the forelimb representation area of the sensorimotor cortex (FL-SMC) in adult rats causes over-reliance on the unimpaired forelimb for postural-motor movements, as well as overgrowth of layer V pyramidal cell dendrites in the homotopic cortex of the noninjured hemisphere. The overgrowth appears to be use-dependent because it can be prevented by restricting movements of the unimpaired forelimb. Additionally, restricting the unimpaired forelimb in animals with FL-SMC damage results in significantly greater behavioral dysfunction when examined 2 d after cast removal (compared to that after impaired-limb immobilization, or no limb immobilization). In the present study, the long-term behavioral and anatomical effects of limb immobilization were examined. Animals with FL-SMC lesions were fitted with casts immediately after the lesion that immobilized the impaired forelimb, the unimpaired forelimb, or neither forelimb for 15 d. Immobilization of the nonimpaired forelimb resulted in chronic prevention of dendritic growth and severe and chronic behavioral deficits. In addition, immobilization of the nonimpaired forelimb resulted in a dramatic exaggeration of the neuronal injury, presumably attributable to forced overuse of the impaired limb. Immobilization of the impaired forelimb resulted in no detectable neural changes and in only slightly increased and longer-lasting behavioral asymmetries (compared to nonimmobilized, lesioned animals), presumably attributable to mild disuse of the impaired limb. Immobilization of a single forelimb in nonlesioned rats resulted in no significant behavioral or anatomical changes. Together, these results suggest that although behavioral experience can enhance neural growth after brain injury, the region surrounding the injury may be vulnerable to behavioral pressure during the early postlesion period.

Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

“…This task measures somatosensory dysfunction following injury and is a sensitive measure of limb use asymmetry following unilateral brain injury and stroke [16,17,25]. Animals were tested on post-transplantation days 5 and 12.…”

Fetal Transplants Alter the Development of Function after Spinal Cord Transection in Newborn Rats

“…Training can also improve function (Smith et al, 1982;Lovely et al, 1986;Muir and Steeves, 1997), perhaps in part by eliciting changes in stretch reflex activity that depend on mechanisms intrinsic to the spinal cord itself (Wolpaw and Carp, 1993). There is also evidence, however, that intensive training paradigms can modify neural structures in ways that may have deleterious effects (Jones and Schallert, 1994;Kozlowski et al, 1996).…”

A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

“…Moreover, exposure of rats to task-specific [7,31,32] or nonspecific [10,[33][34][35][36] forelimb activity post-ischemia can improve functional outcomes. Notably, some experimental models of forced limb use in rodents have resulted in increased damage and worsened functional recovery [8,[37][38][39] . The reasons for these discrepancies are unclear, but probably involve interactions between the stroke model used, the intensity of forced use, and the stress inherent in restraint.…”