Award
National Institute of Neurological Disorders and Stroke 5R01NS119166-06
Astrocytic WNK-SPAK-NKCC1 Cascade in White Matter Astrogliosis and Injury
Recipient
Louisiana State University Health Sciences Center Shreveport, Department of Neurology
Award Amount
$450,735.00
Ceiling
$450,735.00
Awarded
March 27, 2026
Identifier
5R01NS119166-06
The NIH-funded project studies molecular mechanisms of white matter damage and cognitive impairment in VCID using mouse models. It focuses on the WNK-SPAK-NKCC1 cascade in astrocytes and tests a novel SPAK inhibitor to reduce brain lesions and cognitive deficits.
Description
This project investigates the activation of the WNK-SPAK-NKCC1 protein complex in white matter tracts and hippocampus using mouse models of vascular contributions to cognitive impairment and dementia (VCID) with chronic bilateral carotid artery stenosis (BCAS). It explores the role of IL-18R1 and NF-κB in astrocytes, and tests a SPAK inhibitor ZT-1a to mitigate brain lesions and cognitive deficits. The study aims to understand molecular mechanisms underlying white matter damage and cognitive impairment in VCID, focusing on astrocyte signaling pathways and potential therapeutic intervention.