title: Therapies negating neuroinflammation after brain trauma.
abstract: Traumatic brain injury (TBI) elicits a complex secondary injury response, with neuroinflammation as a crucial central component. Long thought to be solely a deleterious factor, the neuroinflammatory response has recently been shown to be far more intricate, with both beneficial and detrimental consequences depending on the timing, magnitude and specific immune composition of the response post-injury. Despite extensive preclinical and clinical research into mechanisms of secondary injury after TBI, no effective neuroprotective therapy has been identified, with potential candidates repeatedly proving disappointing in the clinic. The neuroinflammatory response offers a promising avenue for therapeutic targeting, aiming to quell the deleterious consequences without influencing its function in providing a neurotrophic environment supportive of repair. The present review firstly describes the findings of recent clinical trials that aimed to modulate inflammation as a means of neuroprotection. Secondly, we discuss promising multifunctional and single-target anti-inflammatory candidates either currently in trial, or with ample experimental evidence supporting clinical application. This article is part of a Special Issue entitled SI:Brain injury and recovery.
authors.affiliation: Canadian Military and Veterans׳ Clinical Rehabilitation Research Program, Faculty of Rehabilitation Medicine, University of Alberta, 3-48 Corbett Hall, Edmonton, AB, Canada T6G 2G4. Electronic address: hellewel@ualberta.ca.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hellewell
authors.affiliation: Melbourne Brain Centre, Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Melbourne, Australia. Electronic address: Bridgette.Semple@unimelb.edu.au.
authors.forename: Bridgette D
authors.initials: BD
authors.lastname: Semple
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Australian New Zealand Intensive Care Research Centre, Melbourne, Australia; Barrow Neurological Institute, Department of Child Health, University of Arizona, Phoenix, USA. Electronic address: cristina.morganti-kossmann@monash.edu.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Morganti-Kossmann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents
keywords: Chemokine; Cytokine; Neuroinflammation; Neuroprotection; Neurotrauma; Traumatic brain injury