Table of Contents
ABSTRACT
Imagine a time when a patient is rushed into an emergency department having sustained a head injury. Prior to any tests, with only a history, we decide to administer a cocktail of neuroprotective and/or neuro-supportive medications as a boost, to aid this patient in a time-sensitive albeit, trying road to full recovery. It is not dissimilar to giving crystalloids to a burns patient. Arguably, like our Omega-3 fatty acid supplementation for brain health maintenance to the more radical neuroprotective effects of magnesium sulfate on a preterm infant, as well as reducing cerebral vasospasm in eclampsia, the forefront of neuropharmacologic research regarding traumatic brain injury (TBI) has spread over recent years, studying molecular mechanisms in injured and uninjured brains, from mild to severe TBI. Extrapolating from various inflammatory and anti-inflammatory mediators, their cascades, receptors, the environment surrounding the cells of the central nervous system (CNS), and their responses to insults, gives us a glimpse of ways to not only intervene, but help the brain by promoting the beneficial mechanisms and assuaging the detrimental ones. There is great potential to control inflamm-ation, reduce scarring, and as a result, decrease long term neurologic deficits, thus, protecting TBI patients from exper-iencing less than favourable long term outcomes.
Connections between the adaptability of the nervous system post insult and intervention are increasingly being recognized and ways of harnessing this molecular adaptability is a field of molecular therapeutic target research. Internal factors such as genetics, and external factors such as pharmacotherapy interestingly play huge roles separately, additively and possibly synergistically, in guiding the human brain towards a ‘healed state’. This thesis, backed by myriad molecular studies such as the heme oxygenase system and neuroinflammation, effects of approved mainstream drugs on the CNS, pharmacotherapeutic targets like microglia, synapses and pericytes, and clinical trials of nerve growth factor (NGF) administration, suggests that despite the less than palatable outcomes of TBI and low translational researched treatments to clinical practice, we are not far from being equipped to protect the brain from further to long term secondary brain damage, allowing us to reduce the prevalence of neurological deficits over time.
Keywords: pericytes, neurotrophins, targets, repair, neuroinflammation
