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The Role of Substance P Within Traumatic Brain Injury and Implications for Therapy.

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Safwat, Adam 
Helmy, Adel 
Gupta, Arun 


This review examines the role of the neuropeptide substance P within the neuroinflammation that follows traumatic brain injury. It examines it in reference to its preferential receptor, the neurokinin-1 receptor, and explores the evidence for antagonism of this receptor in traumatic brain injury with therapeutic intent. Expression of substance P increases following traumatic brain injury. Subsequent binding to the neurokinin-1 receptor results in neurogenic inflammation, a cause of deleterious secondary effects that include an increased intracranial pressure and poor clinical outcome. In several animal models of TBI, neurokinin-1 receptor antagonism has been shown to reduce brain edema and the resultant rise in intracranial pressure. A brief overview of the history of substance P is presented, alongside an exploration into the chemistry of the neuropeptide with a relevance to its functions within the central nervous system. This review summarizes the scientific and clinical rationale for substance P antagonism as a promising therapy for human TBI.



neurogenic inflammation, neuroinflammation, neurokinin-1 receptor antagonist, substance P, traumatic brain injury, Animals, Humans, Substance P, Receptors, Neurokinin-1, Brain Injuries, Traumatic, Central Nervous System, Brain Edema

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J Neurotrauma

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Mary Ann Liebert Inc
Medical Research Council (G0802251)
Medical Research Council (G0802251/1)
Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no. G0802251), the NIHR Biomedical Research Centre and the NIHR Brain Injury MedTech Co-operative. PresSura Neuro (Melbourne, Australia) are funding staff and study costs for the PANGEA drug study.