Combining Multiple Types of Motor Rehabilitation Enhances Skilled Forelimb Use Following Experimental Traumatic Brain Injury in Rats

Abstract

Background Neuroplasticity and neurorehabilitation have been extensively studied in animal models of stroke to guide clinical rehabilitation of stroke patients. Similar studies focused on traumatic brain injury (TBI) are lacking. Objective The current study was designed to examine the effects of individual and combined rehabilitative approaches, previously shown to be beneficial following stroke, in an animal model of moderate/severe TBI, the controlled cortical impact (CCI). Methods Rats received a unilateral CCI, followed by reach training, voluntary exercise, or unimpaired forelimb constraint, alone or in combination. Forelimb function was assessed at different time points post-CCI by tests of skilled reaching, motor coordination, and asymmetrical limb use. Results Following CCI, skilled reaching and motor coordination were significantly enhanced by combinations of rehabilitation strategies, not by individual approaches. The return of symmetrical limb use benefited from forelimb constraint alone. None of the rehabilitation strategies affected the size of injury, suggesting that enhanced behavioral function was not a result of neuroprotection. Conclusions The current study has provided evidence that individual rehabilitation strategies shown to be beneficial in animal models of stroke are not similarly sufficient to enhance behavioral outcome in a model of TBI. Motor rehabilitation strategies for TBI patients may need to be more intense and varied. Future basic science studies exploring the underlying mechanisms of combined rehabilitation approaches in TBI as well as clinical studies comparing rehabilitation approaches for stroke versus TBI would prove fruitful.

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

“…CCI to the CMC resulted in major impairments in both groups, as assessed at day 3. Similar to our recently published findings, 15 the combination RT regimen that included daily tray reaching, exercise, and forelimb constraint significantly improved forelimb function on the SPR task, compared to untrained controls, after CMC focused CCIs. There was a significant Group·Day interaction effect (F (7,168) = 9.72; p < 0.0001).…”

“…Two of our recent studies indicate that this assumption is flawed. 14,15 After a unilateral controlled cortical impact (CCI) over the caudal motor cortex (CMC) in rats, there are long-term forelimb impairments, similar to what is found following other models of damage to the motor cortex; however, we found that neural remodeling was severely blunted post-CCI compared to similarly placed and sized ischemic lesions.…”

“…8,10,17,[19][20][21] However, after CCIs over the CMC, forelimb function on a skilled forelimb reaching task was improved only when animals received reaching practice and voluntary exercise, with or without nonimpaired forelimb constraint. 15 Thus, our data support that the neuroplastic response to injury and the behavioral response to RT post-CCI are not the same as after ischemic damage, despite similar initial behavioral impairments and damage to similar areas of the brain.…”

“…14,[16][17][18] Further, we also recently reported that motor treatments that have been found to improve forelimb function after ischemic stroke (reaching alone and forelimb constraint alone), were not effective post-CCI over the forelimb area of the CMC unless they were combined. 15 Skilled forelimb reaching, voluntary aerobic exercise, and nonimpaired forelimb constraint individually have been shown to enhance recovery or enhance neural plasticity in animal models of stroke and focal lesions. 8,10,17,[19][20][21] However, after CCIs over the CMC, forelimb function on a skilled forelimb reaching task was improved only when animals received reaching practice and voluntary exercise, with or without nonimpaired forelimb constraint.…”

“…Additionally, this timing was previously found to be highly effective in enhancing motor recovery post-CCI. 15 We thus examined the functional integrity of the remaining motor cortex using standard ICMS techniques. Future studies will examine motor map changes induced by potential additive and/or interaction effects of each therapy alone and in combination.…”