ABSTRACT
NSCs (neural stem cells) provide a powerful research tool for the design and discovery of new approaches to cell replacement therapy during brain repair. However, the usefulness of this tool has been particularly obstructed by limited neuronal differentiation of NSCs. Brn-4, a member of the POU domain family of transcription factors, has been previously implicated in the development of neurons by expression analysis. Here, we directly investigated the effects of Brn-4 on the neuronal differentiation and development of NSCs derived from the E13 rat midbrain. We found that Brn-4 knockdown in NSCs resulted in a significant decrease of MAP-2-positive neurons with immature morphology. Overexpression of Brn-4 in NSCs markedly increased the production and maturation of newborn neurons. These results suggest that Brn-4 has a critical role in the neuronal differentiation of mesencephalic NSCs and the maturation of newborn neurons. Brn-4 may be utilized to manipulate NSCs for gene and cell therapy of several neurological diseases.
Subject(s)
Cell Differentiation , Mesencephalon/cytology , Nerve Tissue Proteins/metabolism , Neurons/cytology , Neurons/metabolism , POU Domain Factors/metabolism , Stem Cells/cytology , Animals , Blotting, Western , Clone Cells , Fluorescent Antibody Technique , Luminescent Proteins/metabolism , RNA Interference , Rats , Rats, Sprague-Dawley , Recombinant Proteins/metabolism , Stem Cells/metabolism , TransfectionABSTRACT
OBJECTIVE: To investigate the changes in regional cerebral blood flow (RCBF) and cerebral hemodynamics in patients with dizziness resulted from disorders of the central nervous system. METHOD: Using 133Xe inhalation technique and transcranial Doppler ultrasonography(TCD), we measured RCBF and blood flow velocity in the major cerebral arteries in 86 such patients with dizziness, who were divided into persisting and intermittent groups according to the symptoms. Another 86 normal adult subjects were also included as the control group. All the patients were free from cerebral structural abnormalities as demonstrated by CT or magnetic resonance imaging. RESULT: Decreased RCBF was found in 60.5% of the patients with also lowered cerebral blood flow velocity, and the abnormalities appeared more serious when the dizziness persisted. The RCBF in the cerebral hemisphere and each cerebral lobes, along with the blood velocity in the cerebral arteries, was significantly lower in the 2 patient groups than in the control group. CONCLUSION: Measurement of RCBF and cerebral blood velocity in patients with central nervous system-related dizziness but without cerebral structural changes may facilitate the assessment of the degree of pathological changes in RCBF and hemodynamics in the affected area and help to better understand the patterns of these changes, which may consequently assist clinical decisions on the diagnosis and treatment of the disease.
