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Randomized Controlled Trial
. 2015 Nov-Dec;29(10):989-1000.
doi: 10.1177/1545968315576577. Epub 2015 Mar 11.

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

DeAnna L Adkins  1 , Lindsay Ferguson  2 , Steven Lance  2 , Aleksandr Pevtsov  2 , Kevin McDonough  2 , Justin Stamschror  2 , Theresa A Jones  3 , Dorothy A Kozlowski  4
Affiliations
Randomized Controlled Trial

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

DeAnna L Adkins et al. Neurorehabil Neural Repair. 2015 Nov-Dec.

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.

Keywords: constraint-induced movement therapy; controlled cortical impact; exercise; motor rehabilitation; neuroplasticity; recovery of function.

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Conflict of interest statement

Declaration of Conflicting Interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ICMJE Uniform Disclosure Form for Potential Conflicts of Interest: Dr Kozlowski reports a grant from US Department of Defense during the conduct of the study.

Figures

Figure 1
Figure 1
(Top) Rehabilitation consisted of single-pellet reaching, exercise, and forelimb constraint alone or in combination administered at different time points and durations following CCI. (Bottom) Behavioral testing (single-pellet reaching, foot fault, and limb use) was administered at baseline (day 0) and at different time points postinjury (red arrows). Rats were killed humanely for histology on day 43.
Figure 2
Figure 2
(A) Rats that received a combination of reaching and exercise (#CCI + RE) or reaching, exercise, and constraint (*CCI + REC) showed enhanced reaching behaviors compared with injured animals without rehabilitation (#P < .05, *P < .01). (B) Injured animals without rehabilitation (CCI) showed progressively more abnormal reaching behaviors over time, whereas all rehabilitation strategies reduced abnormal compensatory reaching behaviors compared with CCI: §CCI + R (P < .0001); ŦCCI + C (P < .0001); #CCI + RE (P < .01); and *CCI + REC (P < .0001). Abbreviation: CCI, controlled cortical impact.
Figure 3
Figure 3
Reliance on the forelimb ipsilateral to injury was significantly increased by CCI. A recovery to symmetrical forelimb use was seen in rats that received forelimb constraint but not in any of the other rehabilitation groups (ŦCCI + C vs CCI, P < .05). Abbreviations: CCI, controlled cortical impact; R, reaching; E, exercise; C, constraint.
Figure 4
Figure 4
Percentage contralateral forelimb faults were significantly reduced in rats that received all 3 rehabilitation regimens (*CCI + REC vs CCI, P < .05). Abbreviations: CCI, controlled cortical impact; R, reaching; E, exercise; C, constraint.
Figure 5
Figure 5
(Top) Volume of remaining cortex is significantly reduced in all injury groups compared with sham (¥P < .05). There were no significant differences in contusion size between treatment groups. (Bottom) Coronal sections representing injury size and location from 0.5 to 2.0 mm anterior to the bregma. Abbreviations: CCI, contusion; R, reaching; E, exercise; C, constraint; CC, corpus callosum; ST, striatum (scale bar = 250 μm).
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