Functional Recovery of the Rat Somatosensory Cortex Following Peripheral Nerve Injury

Previous functional Magnetic Resonance Imaging (fMRI) studies using rats with denervated fore- and hindpaws implicated changes in cortical-cortical communication following peripheral nerve injury. When these denervated rats were stimulated in the intact limb, cortical activity was observed not only in the contralateral (healthy) cortex but in the ipsilateral (deprived) cortex as well. Further studies using high resolution fMRI, electrophysiology, and in vivo juxtacellular labeling techniques showed that peripheral nerve injury is followed by increased inhibitory activity in the deprived cortex, which may be mediated by cortical-cortical interactions. These inhibitory interactions are thought to hinder rehabilitation following peripheral nerve injury.

The goal of this summer's experiments was to test the hypothesis that cortical-cortical inhibition slows recovery from peripheral nerve injury. A multiple nerve crush model, in which rats underwent three nerve crushes of the forepaw median, ulnar, and radial nerves over three weeks, was applied to test this hypothesis. It has been previously demonstrated that following multiple nerve crushes, full regeneration still occurs. Somatosensory Evoked Potentials (SEPs) were used to measure average neuronal activity over the forepaw representation of the somatosensory cortex following forepaw stimulation. Twenty-five rats were studied with SEP at different time points following the nerve crushes to determine the impact of injury on cortical recovery. SEPs were performed on the multiple crush rats at seven and ten weeks following the first crush. These results were compared to the SEPs from control rats that did not undergo any injury. To determine whether increased inhibition mediated by the healthy cortex hinders recovery of the deprived cortex, a group of rats with cortical ablations in the cortex contralateral to the healthy forepaw was also studied with SEP. SEP from rats with ablations only and multiple crush rats with ablations were tested at similar time points to the rats that underwent only the multiple crush. If our hypothesis were correct, then the rats with the cortical ablations should display normal SEPs more quickly than those without ablations because we hypothesized that the ablation would remove or decrease the inhibition from the deprived cortex.

Consistent with previous results from our lab, we found that in the weeks following multiple crush, the healthy cortex exhibits higher neuronal activity. Ten to eleven weeks following the crushes, the activity of the healthy cortex seems to return to the level observed in the control rats. The SEPs of the multiple crush rats after seven and ten weeks as well as the SEPs from the multiple crush rats with ablations after seven weeks were, in fact, larger than those of the controls, for both the intact and the deprived forepaw. SEP measures the difference in neuronal activity between the right and left cortex. Therefore, the amplitude of SEP signals are complicated to interpret. For example, equal signals on each side could either cancel out, producing no signal at all, or could reinforce, producing a large signal. These difficulties persist in the interpretation of these data-for example, the rats with the ablation and multiple crush exhibited very large activity when the healthy forepaw was stimulated. We are still in the process of finding whether the ablations of the healthy cortex do influence the time needed for the deprived cortex to regain its function.

Future work includes the addition of more rats to each group to improve the consistency of the data. Additionally, new groups may be added at different time points during recovery to further characterize the recovery process. Histology on the forepaw nerves will be performed to follow the regeneration process with immune system markers. The brains of the rats with ablations have been removed and will be studied to determine the correlation between the extent of the ablation in the healthy cortex and the degree of recovery of the deprived cortex.