The neuroinflammatory response in humans after traumatic brain injury

Smith, C., Gentleman, S.M., Leclercq, P.D., Murray, L.S., Griffin, W.S.T., Graham, D.I. and Nicoll, J.A.R. (2013) The neuroinflammatory response in humans after traumatic brain injury. Neuropathology and Applied Neurobiology, 39 (6), 654-666. (doi:10.1111/nan.12008). (PMID:23231074)

Abstract

Aims: Traumatic brain injury is a significant cause of morbidity and mortality worldwide. An epidemiological association between head injury and long-term cognitive decline has been described for many years and recent clinical studies have highlighted functional impairment within 12 months of a mild head injury. In addition chronic traumatic encephalopathy is a recently described condition in cases of repetitive head injury. There are shared mechanisms between traumatic brain injury and Alzheimer's disease, and it has been hypothesized that neuroinflammation, in the form of microglial activation, may be a mechanism underlying chronic neurodegenerative processes after traumatic brain injury.

Methods: This study assessed the microglial reaction after head injury in a range of ages and survival periods, from <24-h survival through to 47-year survival. Immunohistochemistry for reactive microglia (CD68 and CR3/43) was performed on human autopsy brain tissue and assessed ‘blind’ by quantitative image analysis. Head injury cases were compared with age matched controls, and within the traumatic brain injury group cases with diffuse traumatic axonal injury were compared with cases without diffuse traumatic axonal injury.

Results: A major finding was a neuroinflammatory response that develops within the first week and persists for several months after traumatic brain injury, but has returned to control levels after several years. In cases with diffuse traumatic axonal injury the microglial reaction is particularly pronounced in the white matter.

Conclusions: These results demonstrate that prolonged microglial activation is a feature of traumatic brain injury, but that the neuroinflammatory response returns to control levels after several years.

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Contributors

Author: J.A.R. Nicoll

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