Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches
Abstract Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS injury is comprised of primary and secondary injury. Inflammatory secondary injury is inc...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03340-7 |
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| author | Dmitriy Lapin Archna Sharma Ping Wang |
| author_facet | Dmitriy Lapin Archna Sharma Ping Wang |
| author_sort | Dmitriy Lapin |
| collection | DOAJ |
| description | Abstract Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS injury is comprised of primary and secondary injury. Inflammatory secondary injury is incited by damage-associated molecular patterns (DAMPs) which signal a variety of resident CNS cells and infiltrating immune cells. Extracellular cold-inducible RNA-binding protein (eCIRP) is a DAMP which acts through multiple immune and non-immune cells to promote inflammation. Despite the well-established role of eCIRP in systemic and sterile inflammation, its role in CNS injury is less elucidated. Recent literature suggests that eCIRP is a pleiotropic inflammatory mediator in CNS injury. eCIRP is also being evaluated as a clinical biomarker to indicate prognosis in CNS injuries. This review provides a broad overview of CNS injury, with a focus on immune-mediated secondary injury and neuroinflammation. We then review what is known about eCIRP in CNS injury, and its known mechanisms in both CNS and non-CNS cells, identifying opportunities for further study. We also explore eCIRP’s potential as a prognostic marker of CNS injury severity and outcome. Next, we provide an overview of eCIRP-targeting therapeutics and suggest strategies to develop these agents to ameliorate CNS injury. Finally, we emphasize exploring novel molecular mechanisms, aside from neuroinflammation, by which eCIRP acts as a critical mediator with significant potential as a therapeutic target and prognostic biomarker in CNS injury. |
| format | Article |
| id | doaj-art-f2c72d340a2a4ced8b39babd22765f50 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-f2c72d340a2a4ced8b39babd22765f502025-01-26T12:45:20ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111610.1186/s12974-025-03340-7Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approachesDmitriy Lapin0Archna Sharma1Ping Wang2Center for Immunology and Inflammation, The Feinstein Institutes for Medical ResearchCenter for Immunology and Inflammation, The Feinstein Institutes for Medical ResearchCenter for Immunology and Inflammation, The Feinstein Institutes for Medical ResearchAbstract Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS injury is comprised of primary and secondary injury. Inflammatory secondary injury is incited by damage-associated molecular patterns (DAMPs) which signal a variety of resident CNS cells and infiltrating immune cells. Extracellular cold-inducible RNA-binding protein (eCIRP) is a DAMP which acts through multiple immune and non-immune cells to promote inflammation. Despite the well-established role of eCIRP in systemic and sterile inflammation, its role in CNS injury is less elucidated. Recent literature suggests that eCIRP is a pleiotropic inflammatory mediator in CNS injury. eCIRP is also being evaluated as a clinical biomarker to indicate prognosis in CNS injuries. This review provides a broad overview of CNS injury, with a focus on immune-mediated secondary injury and neuroinflammation. We then review what is known about eCIRP in CNS injury, and its known mechanisms in both CNS and non-CNS cells, identifying opportunities for further study. We also explore eCIRP’s potential as a prognostic marker of CNS injury severity and outcome. Next, we provide an overview of eCIRP-targeting therapeutics and suggest strategies to develop these agents to ameliorate CNS injury. Finally, we emphasize exploring novel molecular mechanisms, aside from neuroinflammation, by which eCIRP acts as a critical mediator with significant potential as a therapeutic target and prognostic biomarker in CNS injury.https://doi.org/10.1186/s12974-025-03340-7CNS injuryTraumatic brain injuryIschemic strokeIntracerebral hemorrhageNeuronal deathDAMPs |
| spellingShingle | Dmitriy Lapin Archna Sharma Ping Wang Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches Journal of Neuroinflammation CNS injury Traumatic brain injury Ischemic stroke Intracerebral hemorrhage Neuronal death DAMPs |
| title | Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches |
| title_full | Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches |
| title_fullStr | Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches |
| title_full_unstemmed | Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches |
| title_short | Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches |
| title_sort | extracellular cold inducible rna binding protein in cns injury molecular insights and therapeutic approaches |
| topic | CNS injury Traumatic brain injury Ischemic stroke Intracerebral hemorrhage Neuronal death DAMPs |
| url | https://doi.org/10.1186/s12974-025-03340-7 |
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