Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat.

PURPOSE: Recovery is limited following traumatic brain injury (TBI) since injured axons regenerate poorly and replacement of lost cells is minimal. Behavioral improvements could instead be due to plasticity of uninjured brain regions. We hypothesized that plasticity of the uninjured hemisphere occurs contralateral to a focal TBI in the adult rat. Thus, we performed cortical mapping of the cortex contralateral to the TBI using intracortical microstimulation (ICMS). METHODS: A focal TBI was induced using the weight-drop technique (n = 5) and sham-injured animals were used as controls (n = 4). At five weeks post-injury, ICMS was used to map the motor area contralateral to the injury. Motor responses were detected by visual inspection and electromyography (EMG). RESULTS: In sham- and brain-injured animals, numerous fore- and hindlimb motor responses contralateral to the stimulation (ipsilateral to the injury) were obtained. Compared to sham-injured controls, there was a markedly increased (p < 0.05) number of fore- and hindlimb responses ipsilateral to the stimulation after TBI. CONCLUSION: Following focal TBI in the rat, our data suggest reorganization of cortical and/or subcortical regions in the uninjured hemisphere contralateral to a focal TBI leading to an altered responsiveness to ICMS. Although we cannot exclude that these changes are maladaptive, it is plausible that this plasticity process positively influences motor recovery after TBI.

Functional and histological outcome after focal traumatic brain injury is not improved in conditional EphA4 knockout mice.

We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or sham injury and found it to be downregulated in the hippocampus (p<0.05) but not the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the behavioral and histological outcome following CCI using WT mice and Emx1-Cre-driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent in the hippocampus and markedly reduced in the cortical regions from embryonic day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had similar learning and memory abilities at 3 weeks post-TBI compared to WT controls, although brain-injured animals performed worse than sham-injured controls (p<0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod and cylinder tests of motor function up to 29 days post-injury. TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p<0.05) and hippocampal sprouting (Timm stain, p<0.05) and induced a marked loss of hemispheric tissue (p<0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.