Date of Award

Spring 2017

Document Type

Open Access Thesis


College of Arts & Sciences


Math & Science

Degree Name

Biology, BA

First Supervisor

Dr. Rici Hallstrand


Human infants born prematurely between 23-32 weeks have a predisposition toward sustaining white matter injury (WMI). In survivors of preterm birth, hypoxic-ischemic (H-I) damage to the cerebral white matter is the leading cause of a spectrum of neurological and motor deficits and in severe cases, cerebral palsy (CP). H-I triggers extracellular matrix (ECM) breakdown leading to production of inhibitory ECM components. H-I also induces vigorous proliferation of oligodendrocyte progenitor cells (OPCs) leading to accumulation of the pre-oligodendrocytes (preOLs). However, these preOLs fail to differentiate and generate myelin producing oligodendrocytes (OLs). Mechanistically, ECM breakdown blocks repair and regeneration of myelin following WMI as hyaluronic acid (HA), a major component of the brain ECM, is digested into bioactive fragments (fHA). Previous studies have shown that following WMI, HA degraded by PH20 hyaluronidase to fHA prevents differentiation of preOLs to mature OLs, but whether fHA plays a role in H-I mediated OPC proliferation is unknown. To determine if hyaluronidase plays a role in vivo to promote OPC proliferation, we utilized a neonatal rodent preterm model of H-I and a new selective PH20 inhibitor, SuBr3. Our hypothesis tests whether SuBr3 mediated inhibition of PH20 activity will also attenuate the OPC proliferation response observed after neonatal WMI. We found a significant decrease in Ki67+ cells in WMI lesions in the SuBr3 treated animals relative to all other control groups, suggesting total cell proliferation was attenuated and mediated by PH20 hyaluronidase activity. Future experiments will analyze whether SuBr3 treatment also results in changes in the total pool of OL lineage cells and preOLs in the WMI lesions.

Included in

Biology Commons