reduced creatine kinase b activity in multiple sclerosis normal appearing white matter肌酸激酶b减少活动正常白质出现多发性硬化症.pdfVIP

Reduced Creatine Kinase B Activity in Multiple Sclerosis Normal Appearing White Matter 1. 1. 2,3 1 1,4 Christel Steen , Nadine Wilczak , Johannes M. Hoogduin , Marcus Koch , Jacques De Keyser * 1 Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 2 Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands, 3 BCN-Neuroimaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 4 Department of Neurology, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium Abstract Background: Two studies using 31P-magnetic resonance spectroscopy (MRS) reported enhanced phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but this finding could not be properly explained. Methodology/Principal Findings: We performed 31P-MRS and 1H-MRS in the NAWM in 36 subjects, including 17 with progressive MS, 9 with benign MS, and 10 healthy controls. Compared to controls, PCr/b-ATP and PCr/total 31P ratios were significantly increased in subjects with progressive MS, but not with benign MS. There was no correlation between PCr ratios and the N-acetylaspartate/creatine ratio, suggesting that elevated PCr levels in NAWM were not secondary to axonal loss. In the central nervous system, PCr is degraded by creatine kinase B (CK-B), which in the white matter is confined to astrocytes. In homogenates of NAWM from 10 subjects with progressive MS and 10 controls without central nervous system disease, we measured CK-B levels with an ELISA, and m