Traumatic brain injury and the sensory cortex using environmental enrichment as a therapeutic option
2017-02-17T00:06:29Z (GMT) by
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, and represents a significant economic burden on society, with patients suffering from TBI often presenting with a number of sensorimotor and cognitive disabilities post-injury. While motor deficits are largely resolved through rehabilitative therapy, sensory and cognitive deficits are known to persist for up to months and years post-TBI as there is currently no established rehabilitation for these disabilities. One of the main aims of the present thesis is to investigate changes in neuronal function across different sensory cortical layers after diffuse TBI, as it is likely that abnormal neuronal function in sensory cortex is responsible for the persistent sensory and cognitive deficits reported after injury. We used the rat whisker barrel cortex as a sensory systems model due to its highly organised nature, and well-characterised structure and function. Firstly, we found that diffuse TBI induces significant and persistent motor and whisker-specific sensory deficits. Extracellular recordings from the sensory cortex revealed significant neuronal hyperexcitation in the supragranular layers of cortex post-TBI, mainly in response to complex, ‘naturalistic’ whisker stimulation patterns. These results suggest that injury-induced changes in the processing of incoming sensory information could underlie changes in sensory behaviour, and that these deficits may be better identified using diagnostic tests which specifically examine complex sensory behaviours. Following this, we aimed to explore the use of environmental enrichment (EE) as a putative therapy to ameliorate TBI-induced deficits in sensory behaviour and abnormal neuronal function. We first investigated the effect of long-term (8 weeks) EE on neuronal function in normal (Sham) animals and compared its effects with neuronal function in normal animals housed in standard laboratory conditions (single housed, standard cage sizes). EE housing induced significant increases in neuronal activity across most layers of the sensory cortex, in response to both simple, and complex whisker motion stimuli. These data demonstrate that EE is capable of inducing long-term changes in neuronal plasticity in the sensory cortex. Finally, we aimed to investigate whether EE-induced neuronal plasticity could ameliorate cortical hyperexcitability in the long-term post-TBI, and whether these changes, if any, would be reflected by an improvement in sensory behaviour. Results from this study showed that EE exposure post-TBI resulted in a restoration of neuronal activity in supragranular layers of the sensory cortex, whereby neurons were no longer hyperexcitable at 8-10 weeks after injury. We also demonstrated a reduction in sensory hypersensitivity after EE-exposure in injured animals, possibly reflecting the protective effect of EE on neuronal activity. The work presented in this thesis has, for the first time, provided an understanding of changes in neuronal function in sensory cortex in the long-term after TBI, and related these changes to sensorimotor morbidities. The use of EE as a rehabilitative treatment for these TBI-induced changes has proved to be quite successful in the setting of the current thesis, with the results from these studies providing a solid foundation upon which to further investigate the underlying mechanisms involved in the restorative effect of EE.