Review Article
Guilty Molecules, Guilty Minds? The Conflicting Roles of the Innate Immune Response to Traumatic Brain Injury
Table 1
Key studies highlighting the dual roles of proinflammatory cytokines after traumatic brain injury.
(a) |
| IL-1β |
| Finding | Clinical/experimental | Experimental setting | Reference |
| Acutely upregulated after TBI | Clinical | Cerebral microdialysis; adult and pediatric patient CSF | [100, 102, 116, 117] | Peripheral administration after TBI results in larger lesions and impaired behavioural outcomes | Experimental (rat) | Fluid percussion injury | [118] | Expression exacerbated and prolonged by secondary insult | Experimental (rat) | Diffuse axonal injury with posttraumatic hypoxia | [27] | Causes BBB dysfunction in vivo | Experimental (rat; in vitro) | Cerebral endothelial cells | [119] |
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(b) |
| TNF |
| Finding | Clinical/experimental | Study methodology | Reference |
| High levels observed acutely after injury | Clinical | Cerebral microdialysis, adult patient CSF | N [102, 120, 121] | Acutely upregulated in rats after focal TBI | Experimental (rat) | Controlled cortical injury; lateral fluid percussion | [115, 122] | Administration causes BBB dysfunction and increased recruitment of peripheral leukocytes | Experimental (rat, newborn piglet, rat; in vitro) | Healthy animals/cerebral endothelial cells | N [119, 123, 124] | Inhibition of TNF ameliorates BBB dysfunction | Experimental (rat) | Controlled cortical injury | [125] | Deficiency of TNF/TNF-R causes exacerbated BBB damage and impairs long-term recovery | Experimental (mouse) | Controlled cortical injury | N [126, 127] | Expression exacerbated and prolonged by secondary insult | Experimental (rat) | Diffuse axonal injury with posttraumatic hypoxia | [27] |
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(c) |
| IL-6 |
| Finding | Clinical/experimental | Study methodology | Reference |
| CSF levels correlate with improved outcome | Clinical | Adult and pediatric patient CSF | [128, 129] | Production within 24 h localised to neurons | Experimental (rat) | Diffuse axonal injury | [130] | IL-6 deficient mice have heightened neurodegeneration, increased oxidative stress, poor behavioural recovery | Experimental (mouse) | Controlled cortical injury; aseptic cerebral injury | [158–160] |
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(d) |
| GM-CSF |
| Finding | Clinical/experimental | Study methodology | Reference |
| Significantly upregulated in brain tissue within minutes of TBI | Clinical | Postmortem brain tissue | [131] | Promotes neuronal stem cell differentiation in vitro | Experimental (rat; in vitro) | Neural stem cell culture | [132] | Promotes tissue sparing when administered in conjunction with IL-3 | Experimental (rat) | Stab-wound injury | [133] | Minimises tissue damage and promotes behavioural recovery | Experimental (rat) | Spinal cord contusion | [134, 135] |
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