Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury
Year: 2024
Type: article
Abstract: Traumatic injury to the spinal cord (SCI) results in immediate necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progress hemorrhagic necrosis (PHN) and excessive excitation are the primary sources of neural injury triggered by various insults, causing neuronal cytotoxicity and the gradual enlargement of lesions. Recent approaches have involved blocking TRPM4, a contributor to PHN, using the sulfonylurea (SUR) subunits regulator glibenclamide. However, since SUR subunits are expressed in both neurons and glial cells in the spinal cord and sensory neurons, forming functional K ATP channels, the use of glibenclamide can exacerbate the development of SCI-induced chronic pain. In this study, we explored a treatment strategy involving the administration of glibenclamide, which suppresses PHN, and diazoxide, which protects against neuronal excitation and inflammation, at different time intervals post-SCI. Our goal is to determine whether this approach significantly enhances both sensory and motor function. Contusive SCI was induced at spinal segment T10 in adult male and female rats. Immunostaining, electrophysiological recording in vitro , spectrophotometric assay, Western blot, and behavioral tests were performed to detect the outcomes. Results showed that the timed application of glibenclamide and diazoxide at various post-SCI time points significantly improved locomotor function and mitigated the development of SCI-induced chronic pain. These preclinical studies introduce a promising treatment strategy for addressing SCI-induced dysfunction.
Source: Frontiers in Pharmacology
Authors: Guo-Ying Xu, Manjit Maskey, Zizhen Wu, Qing Yang
Institution: The University of Texas Medical Branch at Galveston
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
Awards: G1302989847, G1363848847, G1739342530, Neuroprotective Effects of Targeting KCNQ/Kv7 Channels after Spinal Cord Injury, G3371282615, G5435005314, G5831653103, G5850682332, (PQ9) A NOVEL MECHANISM OF PACLITAXEL-INDUCED PERIPHERAL NEUROPATHY AND POTENTIAL TREATMENT, G842818689, G8851710377, G9000083000
OpenAlex ID: W4401232211