Search

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.

Progressive neurodegeneration following traumatic brain injury (TBI) involves the Fas and TNF-receptor1 protein systems which have been implicated in mediating delayed cell death. In this study, we used two approaches to assess whether inhibition of these pathways reduced secondary brain damage and neurological deficits after TBI. Firstly, we investigated whether the expression of non-functional Fas in lpr mice subjected to TBI altered tissue damage and neurological outcome. Compared to wild-type, lpr mice showed improved neurological deficit (p=0.0009), decreased lesion volume (p=0.017), number of TUNEL+ cells (p=0.011) and caspase-3+ cells (p=0.007). Changes in cellular inflammation and cytokine production were also compared between mouse strains. Accumulation of macrophages/microglia occurred earlier in lpr mice, likely due to enhanced production of the chemotactic mediators IL-12(p40) and MCP-1 (p