# Role of KCC2 in sympathetic dysfunction after spinal cord injury

> **NIH NIH F31** · DREXEL UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
 Following spinal cord injury (SCI) at or above thoracic level 6 (T6), descending supraspinal control over
the spinal neurons associated with sympathetic function is severed. This, along with plasticity within these
neurons themselves, results in exaggerated sympathetic reflexes known as sympathetic hyperreflexia. This
increase in sympathetic activity following SCI causes severe dysfunction of organs receiving sympathetic input,
such as the spleen and vasculature. This contributes to cardiovascular disease and immune dysfunction, two
leading causes of morbidity and mortality in the SCI population. Therefore, increasing understanding of the
mechanisms underlying this plasticity may identify a possible therapeutic for sympathetic hyperreflexia that would
enormously benefit SCI individuals. SCI-induced reduction of receptor cation-chloride cotransporter type 2
(KCC2) in neuronal membranes disrupts chloride homeostasis to decrease synaptic inhibition and has been
implicated in heightened spinal motor reflexes after SCI. Whether KCC2 contributes to sympathetic hyperreflexia
after SCI is not known. We theorize that SCI results in loss of KCC2 in the membrane of spinal neurons
associated with sympathetic function to contribute to sympathetic hyperreflexia. We also postulate that the loss
of KCC2 in the neuronal membrane results from activation of NF-B, a transcription factor that is downstream of
multiple pro-inflammatory cytokines known to be increased following SCI. This proposal will focus on the
hypothesis that hyperexcitability of spinal, sympathetically-associated neurons after SCI is due to downregulation
of KCC2 expression via increased NF-B activation. The primary goals of this proposal are to: 1) investigate
KCC2 in the development of sympathetic hyperreflexia following SCI and if enhancing KCC2 function mitigates
sympathetic hyperreflexia (Aim 1); 2) determine if SCI-induced KCC2 downregulation occurs via NF-B (Aim 2).

## Key facts

- **NIH application ID:** 10998726
- **Project number:** 1F31NS139676-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Mariah J Wulf
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998726

## Citation

> US National Institutes of Health, RePORTER application 10998726, Role of KCC2 in sympathetic dysfunction after spinal cord injury (1F31NS139676-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10998726. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*