# Targeting Sur1-Trpm4 in sepsis-induced brain injury

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $425,028

## Abstract

Abstract
Sepsis-induced brain injury is associated with an acute deterioration of mental status resulting in long-term
cognitive deficits, increased functional morbidity, and diminution in the quality of life. There are limited
diagnostic adjuncts, and as no targeted therapy is available, clinical management of septic patients with central
nervous system (CNS) symptomatology is limited to the treatment of the underlying infection and optimal
critical care management of shock. Therefore, a better understanding of the pathobiology is needed to define
acute brain derangements in sepsis. We have previously demonstrated that magnetic resonance imaging of
the brain in mice subjected to cecal ligation and puncture (CLP) was notable for an early and marked decrease
in fractional anisotropy consistent with axonal swelling and/or axonal injury that was associated with microglial
activation, and the subsequent development of cytotoxic edema as evidenced by a significant decrease in
apparent diffusion coefficient values four days after CLP. Sulfonylurea receptor -1(Sur1) is a transmembrane
receptor in the ATP binding cassette transporter family ABCC8 that upregulates after CNS injury to form an
obligate association with Ca2+ sensitive transient receptor potential melastatin-4 (Trpm4) resulting in edema.
Our preliminary data demonstrate the upregulation of Sur1 in murine septic brains. In this proposal, in aim 1,
we will determine the temporal correlation between Sur1-Trpm4 expression and edema in the murine septic
brain. In aim 2, we will determine if inhibition of Sur1-Trpm4 is associated with a decrease in microglial
activation and edema, thereby leading to a subsequent improvement in outcomes in a murine CLP model of
sepsis. The availability of an FDA approved Sur1-Trpm4 inhibitor further raises interest in this approach.

## Key facts

- **NIH application ID:** 10193865
- **Project number:** 1R21NS121504-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** RAJESH K. ANEJA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $425,028
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10193865

## Citation

> US National Institutes of Health, RePORTER application 10193865, Targeting Sur1-Trpm4 in sepsis-induced brain injury (1R21NS121504-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10193865. Licensed CC0.

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