# Brain injury rehabilitation modality, regulation, & structural plasticity

> **NIH VA I01** · PHOENIX VA HEALTH CARE SYSTEM · 2020 · —

## Abstract

Project Summary
 Traumatic brain injury (TBI) results from mechanical forces applied to the head. Ensuing cascades of
complex pathophysiology transition the injury event into a disease process. The protracted nature of disease
dissuades continued pharmacological interventions in favor of rehabilitation strategies to alleviate neurological
impairment. The enduring constellation of emotional, somatic, and cognitive impairments degrade quality of life
for the millions of TBI survivors suffering from long-term neurological symptoms, and countless more remain
undiagnosed. For these individuals, including a significant percentage of our Veterans, effective therapeutic
interventions are desperately needed. With this clinical problem in mind, rehabilitation strategies have reported
mixed results, as most have not focused on specific symptomatology or explored cellular processes. In rodent
models of diffuse TBI, a late-onset, long-lasting sensory sensitivity to whisker stimulation develops over time,
similar to the protracted onset of light and sound sensitivity in TBI survivors. In addition, experimental diffuse TBI
causes clinically-relevant impairment in short term, long term, and working memory. Therefore, laboratory
studies provide a platform to evaluate efficacy and mechanism of rehabilitation strategies to mitigate neurological
symptoms after diffuse brain injury. In this proposal, we test the hypothesis that therapeutic efficacy of TBI
rehabilitation depends on regional activation during rehabilitation task performance. It follows that
temporary pharmacological inactivation during rehabilitation would eliminate therapeutic efficacy and associated
transformations to relevant brain circuits. To test the hypothesis, adult, male and female rats receive a diffuse
brain or sham injury by midline fluid percussion. Aim 1 addresses whether tactile exploration and spatial
navigation through a peg forest rehabilitation environment for three weeks after 1 month post-injury alleviates
sensory sensitivity and cognitive impairment at two and three months post-injury. Preliminary data indicate peg
forest rehabilitation improves both neurological symptoms, whereas an open field rehabilitation only improves
sensory sensitivity. Aim 2 identifies brain regions activated by rehabilitation and demonstrates the inactivation
by local GABA-A agonist muscimol administration as measured by cFos expression levels. Aim 3 inactivates
associated brain regions (S1BF, hippocampus) to determine whether regional activation is necessary for
rehabilitation therapeutic efficacy. Aim 4 quantifies rehabilitation-related neuropathology and cellular morphology
in associated sensory and cognitive circuitry. Expected outcomes would show therapeutic efficacy of peg forest
rehabilitation on somatosensory and cognitive outcome measures above open field rehabilitation and caged
control animals, which depended on regional activation and underlying remodeling of circuit structure. The impact
of t...

## Key facts

- **NIH application ID:** 10011596
- **Project number:** 5I01RX002472-03
- **Recipient organization:** PHOENIX VA HEALTH CARE SYSTEM
- **Principal Investigator:** Jonathan Lifshitz
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011596

## Citation

> US National Institutes of Health, RePORTER application 10011596, Brain injury rehabilitation modality, regulation, & structural plasticity (5I01RX002472-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10011596. Licensed CC0.

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