# The role of complement in chronic neuroinflammation and cognitive decline after closed head brain injury

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

## Abstract

Traumatic brain injury (TBI) is a major risk factor for early-onset dementia and Alzheimer’s
Disease among Veterans. 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 interventions that have shown to prevent, stop, or reverse cognitive decline in
Veterans who have experienced either mild or severe TBI. Data from animal models of TBI
indicate a role for the neuroinflammatory response in mediating pathological neurodegeneration
after TBI, but characteristics of the neuroinflammatory response, both spatially in the brain and
temporally in relation to cognitive deficits in chronic TBI, has not been explored. In this context,
we have shown that following TBI in mice, there is a robust neuroinflammatory which is observed
at least 6 months after TBI. We have also shown that the complement system is a prominent
trigger of this neuroinflammatory response after TBI. In this project, we propose to investigate the
hypothesis that post-traumatic complement activation and neuroinflammation, that occurs and
persists in the brain following TBI, leads to failure of compensatory mechanisms in primary
cognitive centers of the brain leading to early onset neurodegeneration that is accelerated in an
Alzheimer’s disease mouse model.

## Key facts

- **NIH application ID:** 10806184
- **Project number:** 5I01RX003958-02
- **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:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806184

## Citation

> US National Institutes of Health, RePORTER application 10806184, The role of complement in chronic neuroinflammation and cognitive decline after closed head brain injury (5I01RX003958-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10806184. Licensed CC0.

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