ABSTRACT
Cerebral small vessel disease and brain white matter injury are worsened by cardiovascular risk factors including obesity. Molecular pathways in cerebral endothelial cells activated by chronic cerebrovascular risk factors alter cell-cell signaling, blocking endogenous and post-ischemic white matter repair. Using cell-specific translating ribosome affinity purification (RiboTag) in white matter endothelia and oligodendrocyte progenitor cells (OPCs), we identify a coordinated interleukin-chemokine signaling cascade within the oligovascular niche of subcortical white matter that is triggered by diet-induced obesity (DIO). DIO induces interleukin-17B (IL-17B) signaling that acts on the cerebral endothelia through IL-17Rb to increase both circulating and local endothelial expression of CXCL5. In white matter endothelia, CXCL5 promotes the association of OPCs with the vasculature and triggers OPC gene expression programs regulating cell migration through chemokine signaling. Targeted blockade of IL-17B reduced vessel-associated OPCs by reducing endothelial CXCL5 expression. In multiple human cohorts, blood levels of CXCL5 function as a diagnostic and prognostic biomarker of vascular cognitive impairment.
Subject(s)
Brain Injuries , White Matter , Mice , Humans , Animals , Interleukin-17/metabolism , White Matter/metabolism , Endothelial Cells/metabolism , Brain/metabolism , Signal Transduction , Brain Injuries/metabolism , Oligodendroglia/metabolism , Chemokine CXCL5/metabolismABSTRACT
Ogilvie's syndrome (acute colonic pseudo-obstruction) is a rare disorder characterized by an acute dilation of the colon measuring greater than 10 centimeters. Common symptoms associated with Ogilvie's include abdominal distension, abdominal pain, nausea, vomiting, constipation, and diarrhea. This report presents an uncommon case of a quadriplegic presenting to the emergency department with complaints of abdominal distention. Computed tomography and radiographic imaging studies were consistent with Ogilvie's syndrome. The patient was admitted to the hospital and started on stool softeners and bowel rest with resolution of symptoms. Topics: Ogilvie's syndrome, quadriplegic, abdominal distension, colonic pseudo-obstruction.
