Mesenchymal Stem Cells Prevent Hydrocephalus After Severe Intraventricular Hemorrhage

Abstract

Background and Purpose— Severe intraventricular hemorrhage (IVH) in premature infants and the ensuing posthemorrhagic hydrocephalus cause significant mortality and neurological disabilities, and there are currently no effective therapies. This study determined whether intraventricular transplantation of human umbilical cord blood-derived mesenchymal stem cells prevents posthemorrhagic hydrocephalus development and attenuates brain damage after severe IVH in newborn rats. Methods— To induce severe IVH, 100 μL of blood was injected into each lateral ventricle of postnatal day 4 (P4) Sprague-Dawley rats. Human umbilical cord blood-derived mesenchymal stem cells or fibroblasts (1×10 5 ) were transplanted intraventricularly under stereotaxic guidance at P6. Serial brain MRI and behavioral function tests, such as the negative geotaxis test and rotarod test, were performed. At P32, brain tissue and cerebrospinal fluid were obtained for histological and biochemical analyses. Results— Intraventricular transplantation of umbilical cord blood-derived mesenchymal stem cells, but not fibroblasts, prevented posthemorrhagic hydrocephalus development and significantly attenuated impairment on behavioral tests; the increased terminal deoxynycleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling-positive cells; increased expression of inflammatory cytokines, such as interleukin-1α, interleukin-1β, interleukin-6, and tumor necrosis factor-α; increased astrogliosis; and reduced corpus callosal thickness and myelin basic protein expression after inducing severe IVH. Conclusions— Intraventricular transplantation of umbilical cord blood-derived mesenchymal stem cells significantly attenuated the posthemorrhagic hydrocephalus and brain injury after IVH. This neuroprotective mechanism appears to be mediated by the anti-inflammatory effects of these cells.