Contributions of Interleukin-1 Receptor Signaling in Traumatic Brain Injury

Thome, Jason G.; Reeder, Evan L.; Collins, Sean M.; Gopalan, Poornima; Robson, Matthew J.

doi:10.3389/fnbeh.2019.00287

Cited by 24 publications

(13 citation statements)

References 84 publications

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“…Further, IL-1 is associated with an increased risk for developing post-traumatic epilepsy (185,186), and blocking IL-1 signaling reduces lesion size, neurodegeneration, and improves behavior (187)(188)(189). For review of IL-1 therapies see (190,191).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

et al. 2021

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Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

et al. 2021

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“…IL-1 inhibitors: IL-1 receptor antagonist (IL-1ra) (Anakinra, recombinant human IL-1ra, rhIL-1ra): Both IL-1α and IL-1β bind to IL-1 receptor type 1 (IL-1r1) and initiate signaling. IL-1ra is an endogenous antagonist of the IL-1r1 and blocks receptor activation by IL-1 [ 265 ]. IL-1ra overexpressing transgenic mice showed improved neurological functions with a delayed secretion of pro-inflammatory cytokines in a closed-head injury (CHI) model [ 266 ].…”

Section: Inflammationmentioning

confidence: 99%

Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions

et al. 2020

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Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury.

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“…IL-1ra is an endogenous anti-inflammatory cytokine that binds unproductively to the IL-1 receptor 1 (IL1R1), thereby blocking signaling by two pro-inflammatory cytokines IL-1α and IL-1β. The FDA has approved an altered form of human IL-1ra in the form of anakinra for use in peripheral inflammatory disorders like rheumatoid arthritis [ 17 ]. In the CNS, both of these cytokines, acting through IL1R1s on astrocytes, endothelial cells, and neurons, initiate transcription of multiple pro-inflammatory cytokines, including TNFα, leading to reactive gliosis and enhanced neuronal excitability following such insults as traumatic brain injury.…”

Section: Discussionmentioning

confidence: 99%

Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy

et al. 2021

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Background The underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomarkers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP. Their presence has been investigated in plasma and umbilical cord blood but not in cerebrospinal fluid (CSF). Methods A clinical CP sample was recruited using a single-time point cross-sectional design to collect CSF at point-of-care during a standard-of-care surgical procedure (intrathecal pump implant). Patient demographic and clinical characteristics were sourced from medical chart audit. Results Significant (p ≤ 0.001) associations were found among neuroinflammatory, neuroendocrine, and nociceptive analytes with association patterns varying by birth status (term, preterm, extremely preterm). When between birth-group correlations were compared directly, there was a significant difference between preterm and extremely preterm birth subgroups for the correlation between tumour necrosis factor alpha (TNFα) and substance P. Conclusion This investigation shows that CSF can be used to study proteins in CP patients. Differences in inter-correlational patterns among analytes varying by birth status underscores the importance of considering birth status in relation to possible mechanistic differences as indicated by biomarker signatures. Future work should be oriented toward prognostic and predictive validity to continue to parse the heterogeneity of CP’s presentation, pathophysiology, and response to treatment.

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Contributions of Interleukin-1 Receptor Signaling in Traumatic Brain Injury

Cited by 24 publications

References 84 publications

Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions

Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy

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