Identification of Diazoxide Analogues that Stimulate Oligodendrocyte Proliferation

Abstract

Purpose: Up to 30% of low birth weight preterm infants manifest some form of periventricular white matter injury (PWMI) making it the most common form of brain injury affecting premature infants. It is believed that loss of oligodendrocyte progenitor cells (OPCs), which are proliferative cells that develop into myelinating OLs, plays a major role in PWMI causation. Presently, few pharmacological approaches specifically target OPCs resulting in increased proliferation of these cells and increased brain myelination. We discovered that diazoxide (DZ), an activator of ATP-sensitive potassium channels (KATP), promotes OPC proliferation and attenuated hypoxia induced brain injury in neonatal mice. Out of 610 Diazoxide derivatives, compound …