Research Reports - Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention

Brain Behav Immun. 2012 Jun 21

Kumar A, Loane DJ

Traumatic brain injury (TBI) remains one of the leading causes of mortality and
morbidity worldwide, yet despite extensive efforts to develop neuroprotective
therapies for this devastating disorder there have been no successful outcomes in
human clinical trials to date. Following the primary mechanical insult TBI
results in delayed secondary injury events due to neurochemical, metabolic and
cellular changes that account for many of the neurological deficits observed
after TBI. The development of secondary injury represents a window of opportunity
for therapeutic intervention to prevent progressive tissue damage and loss of
function after injury. To establish effective neuroprotective treatments for TBI
it is essential to fully understand the complex cellular and molecular events
that contribute to secondary injury. Neuroinflammation is well established as a
key secondary injury mechanism after TBI, and it has been long considered to
contribute to the damage sustained following brain injury. However, experimental
and clinical research indicates that neuroinflammation after TBI can have both
detrimental and beneficial effects, and these likely differ in the acute and
delayed phases after injury. The key to developing future anti-inflammatory based
neuroprotective treatments for TBI is to minimize the detrimental and neurotoxic
effects of neuroinflammation while promoting the beneficial and neurotrophic
effects, thereby creating optimal conditions for regeneration and repair after
injury. This review outlines how post-traumatic neuroinflammation contributes to
secondary injury after TBI, and discusses the complex and varied responses of the
primary innate immune cells of the brain, microglia, to injury. In addition,
emerging experimental anti-inflammatory and multipotential drug treatment
strategies for TBI are discussed, as well as some of the challenges faced by the
research community to translate promising neuroprotective drug treatments to the

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