# Delayed white matter loss in concussive head injuries and its treatment

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2022 · $255,271

## Abstract

Abstract.
Half of all traumatic brain injuries cause changes in white matter integrity. Whereas progress is being made in
understanding the mechanisms that lead to acute axonal injury, there is an unmet need for therapeutics to
prevent delayed neuronal injury and restore neurological function. We recently demonstrated that the acute
intranasal (IN) administration of the cytokine Leukemia Inhibitory factor (LIF) reduced gliosis, preserved
corpus callosal myelination, preserved neocortical volumes and improved sensorimotor behavior in a
neonatal hypoxic-ischemic brain injury. Here, in a mouse closed head injury (CHI) TBI model, we show that
delayed IN LIF Rx prevents sensorimotor functional decline and reduces anxiety when IN LIF Rx is initiated at
6 wks of recovery. Therefore, our overall hypothesis is that intranasal LIF Rx can decrease neurological
deficits after TBI by preventing delayed white matter injury and nurturing axonal regeneration by inhibiting
SARM1 activation. Unequivocally demonstrating that an intervention is slowing a degenerative process and
nurturing regeneration requires monitoring over time to show that it prevents the evolution of tissue damage
and stimulates regeneration. Therefore, we propose to utilize high resolution multiple modality live animal
magnetic resonance imaging to determine the structural and functional changes in response to IN LIF Rx. We
will complement the in vivo imaging with ex-vivo diffusion tensor imaging studies and will correlate the
findings with histological and neurological functional analyses. These studies will pave the way for future
clinical trials where similar radiological markers can be assessed to prevent delayed white matter injury.
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## Key facts

- **NIH application ID:** 10354469
- **Project number:** 1R21NS125201-01
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Dewan Syed Fahmeed Hyder
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $255,271
- **Award type:** 1
- **Project period:** 2021-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354469

## Citation

> US National Institutes of Health, RePORTER application 10354469, Delayed white matter loss in concussive head injuries and its treatment (1R21NS125201-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10354469. Licensed CC0.

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