BACKGROUND: The transcription factor Oligl is required for oligodendrocyte maturation and demyelinated lesion repair, and is a key regulator of myelinogenesis following ischemia. OBJECTIVE: To examine the efficacy o...BACKGROUND: The transcription factor Oligl is required for oligodendrocyte maturation and demyelinated lesion repair, and is a key regulator of myelinogenesis following ischemia. OBJECTIVE: To examine the efficacy of intraventricular injection of a recombinant adenovirus-expressing Oligl gene (Ad5-Oligl-eGFP) on oligodendrocyte maturation and myelin repair following focal cerebral ischemia. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Department of Neurology, Beijing Friendship Hospital Affiliated to Capital Medical University from January 2007 to March 2008. MATERIALS: Adenovirus and a recombinant adenovirus containing Oiigl gene (Ad5-Oligl) were provided by Vector Gene Technology, China. METHODS: All 50 rats were induced by middle cerebral artery occlusion. A total of 46 rats were successfully induced and were subsequently randomly assigned to a adenovirus (Ad5) group and recombinant adenovirus-expression Oligl gene (Ad5-Oligl) group, with 23 rats per group. One day after middle cerebral artery occlusion, either Ad5-Oligl-eGFP or Ad5-eGFP (10 μL, 2.3 ×10^11/mL) was injected into the lateral ventricle on the ischemic hemisphere. MAIN OUTCOME MEASURES: Adenovirus-mediated Oligl gene expression in vitro and in vivo was measured by reverse transcription-polymerase chain reaction and immunofluorescence, respectively. Myelin basic protein (MBP) levels were evaluated by Western Blot, immunostaining, and electron microscopy. RESULTS: Exogenous Oligl expression was measured at the periventricular zone of the lateral ventricle 1 day after Ad5-Oligl injection. In the Ad5-Oligl-treated group, MBP protein levels and average intensity of MBP-immunoreactivity (-ir) increased 28 days after middle cerebral artery occlusion, compared with the control group (P 〈 0.01, P 〈 0.05). Furthermore, myelinated axonal numbers markedly increased following Ad5-Oligl treatment. CONCLUSION: The present data suggested that Ad5-Oligl gene therapy increased MBP expression and the number of remyelinating axons following cerebral ischemia.展开更多
基金the National Natural Science Foundation of China,No.30570626the Natural Science Foundation of Beijing,No.7082028
文摘BACKGROUND: The transcription factor Oligl is required for oligodendrocyte maturation and demyelinated lesion repair, and is a key regulator of myelinogenesis following ischemia. OBJECTIVE: To examine the efficacy of intraventricular injection of a recombinant adenovirus-expressing Oligl gene (Ad5-Oligl-eGFP) on oligodendrocyte maturation and myelin repair following focal cerebral ischemia. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Department of Neurology, Beijing Friendship Hospital Affiliated to Capital Medical University from January 2007 to March 2008. MATERIALS: Adenovirus and a recombinant adenovirus containing Oiigl gene (Ad5-Oligl) were provided by Vector Gene Technology, China. METHODS: All 50 rats were induced by middle cerebral artery occlusion. A total of 46 rats were successfully induced and were subsequently randomly assigned to a adenovirus (Ad5) group and recombinant adenovirus-expression Oligl gene (Ad5-Oligl) group, with 23 rats per group. One day after middle cerebral artery occlusion, either Ad5-Oligl-eGFP or Ad5-eGFP (10 μL, 2.3 ×10^11/mL) was injected into the lateral ventricle on the ischemic hemisphere. MAIN OUTCOME MEASURES: Adenovirus-mediated Oligl gene expression in vitro and in vivo was measured by reverse transcription-polymerase chain reaction and immunofluorescence, respectively. Myelin basic protein (MBP) levels were evaluated by Western Blot, immunostaining, and electron microscopy. RESULTS: Exogenous Oligl expression was measured at the periventricular zone of the lateral ventricle 1 day after Ad5-Oligl injection. In the Ad5-Oligl-treated group, MBP protein levels and average intensity of MBP-immunoreactivity (-ir) increased 28 days after middle cerebral artery occlusion, compared with the control group (P 〈 0.01, P 〈 0.05). Furthermore, myelinated axonal numbers markedly increased following Ad5-Oligl treatment. CONCLUSION: The present data suggested that Ad5-Oligl gene therapy increased MBP expression and the number of remyelinating axons following cerebral ischemia.