# Optimizing Environmental Enrichment to Model Preclinical Neurorehabilitation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $394,087

## Abstract

Traumatic brain injury (TBI) affects more than 10 million individuals worldwide each year (~ 2.8 million in the
USA) and results in long-term motor and cognitive deficits (e.g., reference learning and executive function). To
combat this significant health care issue a variety of relatively invasive experimental therapeutic strategies
have been attempted and have yielded limited translation to the clinic. Environmental enrichment (EE) is a
non-invasive paradigm that promotes significant cognitive recovery and histological protection after
experimental TBI and has the potential to mimic post-TBI clinical rehabilitation. The parent R01 was crafted to
begin refining and optimizing EE after TBI so that it conformed temporally to clinical neurorehabilitation. The
wealth of data lead to a preclinical model of neurorehabilitation that is temporally like the clinic in the sense that
delaying EE for a week (i.e., rehabilitation) and providing only 4-hr per day (as common in the clinic) shows
significant benefits. Overall, the findings provided significant support for EE as a potential model of
neurorehabilitation, but additional empirical research is essential to learn more about its capabilities and
limitations that ultimately strengthen its validity and applicability. Hence, the goal of this renewal is to utilize our
delayed (7 day) and abbreviated (4 h day) EE model of neurorehabilitation, which we refer to as Rehab, to
address questions that concern physiatrists. Five specific aims that are logical and crucial extensions of the
parent grant are proposed: Aim 1a determine whether motor (beam and rotarod), cognitive (spatial learning &
memory, and executive function using the attentional set shifting test that is analogous to the clinical Wisconsin
card sorting task), and affective (open field test) benefits can be sustained after EE is withdrawn, and if so, for
how long, Aim 1b determine if providing “refresher rehab” after the EE-induced benefits begin to wane will
stabilize or re-strengthen benefits, Aims 2abc determine whether “bridging” delayed EE, which is initiated at 7-
days after TBI, with a) [amantadine {10 mg/kg/day; i.p.}], b) aqua therapy [{two 90 s swim sessions}], or c)
music exposure [(3 h per night of New Age, Ambient, or Classical - Mozart’s sonata for two pianos,
K.448)] as adjunct therapies during the week after TBI will augment recovery relative to non-enriched or Rehab
groups, and Aim 3 evaluate mechanisms for the bridge plus Rehab therapies. Completion of the aims will
further advance a model of neurorehabilitation that mimics the real-world while addressing questions that
continue to concern physiatrists, such as how long do the rehab benefits last once discontinued and can they
be maintained or improved further with supplemental rehab? Can supplemental therapies before full rehab
provide a better outcome? What mechanisms are involved in the effects observed? The refined model will
significantly impact and advance rehabilitation-b...

## Key facts

- **NIH application ID:** 10884279
- **Project number:** 5R01NS084967-09
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** ANTHONY E. KLINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $394,087
- **Award type:** 5
- **Project period:** 2014-05-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884279

## Citation

> US National Institutes of Health, RePORTER application 10884279, Optimizing Environmental Enrichment to Model Preclinical Neurorehabilitation (5R01NS084967-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10884279. Licensed CC0.

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