# The neuroprotective role of proliferative reactive astrocytes in the hippocampus, synapse preservation and regeneration following traumatic brain injury

> **NIH NIH R56** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $554,750

## Abstract

Abstract
 Astrocytes react to brain injury with progressive changes in gene expression, morphological hypertrophy,
and proliferation referred as astrogliosis. The beneficial or detrimental effects of proliferative reactive astrocytes
are constantly under debate, and the underlying molecular mechanisms are poorly understood. Our long-term
goal is to dissect the mechanisms underlying the proliferation of reactive astrocytes and its biological function in
the hippocampus after traumatic brain injury (TBI), and in order to find the vital targets for TBI treatment. The
objective of this grant is to determine the role of platelet-derived growth factor receptor alpha (PDGFR) signaling
in regulating reactive astrocyte proliferation and the neuroprotective effects of proliferative reactive astrocytes in
hippocampus-associated functional outcomes post-trauma. The central hypothesis is proliferative reactive
astrocytes regulated by PDGFR mediated signaling pathway are neuroprotective by favoring synapse
preservation and regeneration following TBI. The rationale underlying this proposal is that completion
mechanism study will provide an ideal tool to study the function of proliferative reactive astrocyte in the
hippocampus and which in turn to identify vital targets for therapeutic intervention aiming at functional
improvement after TBI. The central hypothesis will be addressed with pursuing three specific aims. 1) Determine
the role of proliferative reactive astrocytes on synaptic alteration and functional outcomes following TBI; and
study PDGFR-mediated signaling pathway in reactive astrocyte proliferation; 2) Determine how proliferative
reactive astrocyte play its neuroprotective role in synapse preservation and regeneration following TBI; 3)
Determine the neuroprotective effects of astrocytic BDNF overexpression and long-term treatment with BDNF
agonist, a small molecule 7,8-Dihydroxyflavone (DHF) on synapse preservation/regeneration and function
improvement after TBI. The proposed research is innovative because we reveal for the first time the role of
PDGFRin regulating reactive astrocyte proliferation post-trauma using state-of-art inducible conditional
knockout/knockin technique and discover the neuroprotective aspects of proliferative reactive astrocytes in
injured hippocampus. The results will have an important positive impact because they will augment our
knowledge on the pathophysiology of TBI, and may offer a novel intervention for better TBI treatment by
selectively manipulating reactive astrocytes at the proliferation stage with neuroprotective effects that counteract
synapse loss and facilitate synaptogenesis post-trauma.

## Key facts

- **NIH application ID:** 10928420
- **Project number:** 1R56NS131465-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Xiang Gao
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $554,750
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928420

## Citation

> US National Institutes of Health, RePORTER application 10928420, The neuroprotective role of proliferative reactive astrocytes in the hippocampus, synapse preservation and regeneration following traumatic brain injury (1R56NS131465-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10928420. Licensed CC0.

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