Limited differentiation to neurons and astroglia from neural stem cells in the cortex and striatum after ischemia/hypoxia in the neonatal rat brain.

Abstract

We examined whether progenitor neural stem cells can differentiate successfully into mature neurons and astrocytes in a rat model of neonatal hypoxic-ischemic encephalopathy. Seven-day-old Wistar rats were subjected to hypoxic-ischemic stress. At days 5 to 7 after hypoxic-ischemic stress, 5-bromodeoxyuridine (an early marker of cell proliferation) was injected, and the brains were retrieved at 14, 28, and 42 days after hypoxic-ischemic stress. Immunohistochemical and immunofluorescent studies were carried out for 5-bromodeoxyuridine, neuronal nuclear antigen (a marker protein of matured neuron), and glial fibrillary acidic protein (a protein marker of mature astrocytes). Only 1% of neuronal nuclear antigen-positive and 4.6% of glial fibrillary acidic protein-positive cells could be detected among the 5-bromodeoxyuridine-immunopositive cells in the peri-infarcted area of the cortex and the striatum, respectively, at 14 days after hypoxic-ischemic stress. There were no such double-staining cells at 28 and 42 days after hypoxic-ischemic stress. The intrinsic ability for neurologic self-repair was limited at the maturation step after hypoxic-ischemic stress in the neonatal rat brain.