Aging of the brain was studied by comparing follow-up MRI scans in 554 persons aged 70-82 years. Mean interval time between these scans was three years and scans were looked for changes in cerebral... Show moreAging of the brain was studied by comparing follow-up MRI scans in 554 persons aged 70-82 years. Mean interval time between these scans was three years and scans were looked for changes in cerebral infarcts, white matter lesions, cerebral blood flow, and brain volume. Besides this, the preventive effect of pravastatin on these changes was studied. During the study time there was progression of cerebral infarcts, white matter lesions and there was decline of cerebral blood flow and progression of brain atrophy. Treatment with pravastatin 40 mg/daily did not have a protective effect on these changes. Show less
Activation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of... Show moreActivation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of major histocompatibility complex (MHC) molecules. This enhanced expression results from increased levels of several transcription factors involved in MHC gene expression. In addition, microglial activation in MS is characterized by enhanced motility. We show that the expression of the chemokine receptor CCR5, a mediator of cell movement, is increased on microglia, macrophages and astrocytes in MS lesions. Additionally, we have determined that CCR5 transcription is regulated by the transcription factor CREB-1, which is also involved in MHC gene expression, and is highly expressed in MS lesions. Because of their immunomodulatory properties, statins (cholesterol lowering drugs) are recently being considered as a possible treatment for MS. We have determined that statins decrease expression of amongst others MHC and CCR5 molecules by inhibiting the transport of these molecules to the cell surface. In addition, we show that statins reduce the motility of microglia and inhibit the differentiation of blood-derived monocytes into dendritic cells, indicating that statins indeed affect critical immune functions and might prove to be beneficial for treatment of MS patients. Show less
