# Role of complement in TBI

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2024 · —

## Abstract

Traumatic brain injury (TBI) is a major risk factor for developing neurological disorders.
Cumulative evidence from clinical follow-up of returning Veterans demonstrate at least 2-4 times
higher risk of dementia and cognitive decline compared to matched non-TBI Veterans. The
current interventions for post-TBI dementia are limited, and there are currently no therapies that
have shown to prevent, stop, or reverse cognitive decline in patients who have experienced either
mild or severe TBI. There is increasing evidence that a chronic neuroimmune/inflammatory
response induced by TBI plays a central role in the pathophysiology of neurodegenerative
disorders. However, this response can vary greatly between different types of brain injury and can
vary at different stages after injury. We propose to investigate the neuroimmune/inflammatory
response that occurs and develops chronically after severe focal contusion injury vs. mild diffuse
concussive injury. The complement system is a key mediator of inflammation, and the focus of
this proposal is the role of complement in chronic neuroimmune responses and
neurodegeneration that occurs after these different types of brain insults. Understanding
differences in post-TBI neuroimmune responses, as well as regional differences, will permit the
design of appropriately tailored therapies, including complement inhibitory therapies, according
to the type and stage of injury. Overall, the aims of this proposal are to investigate the role of
complement in pathophysiological regional responses after contusion versus concussive injuries,
to compare neurobehavioral outcomes after contusion versus concussive injuries and determine
associations with post-traumatic neuroinflammation and pathology, and finally to investigate the
role of CNS derived complement vs. peripheral complement, as well as immune cell complement
receptors in chronic pathology after either contusion or concussive injuries.

## Key facts

- **NIH application ID:** 10856905
- **Project number:** 5I01BX004256-06
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** Stephen Tomlinson
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856905

## Citation

> US National Institutes of Health, RePORTER application 10856905, Role of complement in TBI (5I01BX004256-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10856905. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*