# Intrathecal pump delivery of neurotrophins for locomotor recovery after spinal cord injury

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $342,330

## Abstract

Project Summary/Abstract
 Modified fibroblast grafts releasing BDNF or NT-3 neurotrophins into the spinal transection site promote the
recovery of plantar weight-bearing treadmill locomotion in adult spinal cats (even without body-weight
supported training) by increasing the activity of the locomotor center region. Used in combination with body-
weight supported treadmill training, neurotrophins augment the recovery obtained with training and could serve
as a rehabilitative supplement to treadmill training and epidural stimulation. The current delivery method
requires exposing the spinal cord and inserting the cells into the injury site which carries high risks of further
damage to the spinal cord. Our preliminary data show that intrathecal delivery of neurotrophins to the lumbar
area via an implanted mini-pump is just as efficacious at promoting locomotor recovery and leads to increased
interneuronal firing. While these preliminary results are in acutely spinalized animals, recent results with
delivery of neurotrophins via cellular grafts show that delivery of neurotrophins to the spinal cord can re-
engage the locomotor circuitry in chronic spinal cord injury models, suggesting that intrathecal delivery might
re-activate locomotor centers chronically isolated from supraspinal inputs. The choice of neurotrophin used to
re-engage the locomotor circuitry may have implications for the development of neuropathic pain, which is a
significant issue to consider prior to clinical applications. BDNF and NT-3 have different actions on sensory
afferents and dorsal horn’s response to sensory stimuli, with a number of conflicting reports on whether the
neurotrophins enhance or reduce pain responses. Confirming the role of either neurotrophin alone in recovery
is imperative, as is establishing the effects of both neurotrophins on dorsal horn neurons’ responses to
innocuous and noxious stimuli.
 Based on our preliminary data we hypothesize that intrathecal delivery of either neurotrophin (BDNF or NT-
3) will promote treadmill weight-bearing stepping in both acute and chronic models of spinal cord injury by
increasing intermediate zone interneuronal activity in a plastic manner. We predict that either neurotrophin will
reduce the ratio of laminae I-II neurons to laminae III-V neurons responsive to low level stimuli (mechanical
allodynia), but that BDNF will lead to a clear increase in laminae I-II neurons’ response to high-level stimuli
(noxious stimuli).

## Key facts

- **NIH application ID:** 10075991
- **Project number:** 5R01NS110605-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Michel A Lemay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,330
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075991

## Citation

> US National Institutes of Health, RePORTER application 10075991, Intrathecal pump delivery of neurotrophins for locomotor recovery after spinal cord injury (5R01NS110605-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10075991. Licensed CC0.

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