Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of the endothelium and heart-brain connection. This blog is informative only--all medical decisions should be discussed with your own physicians.The posts are searchable---simply type in your topic of interest in the search box at the top left.Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the auto-immune paradigm of MS, and continues the 20 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.To learn how this journey began, read my first post from August, 2009. Be well! Joan
Thursday, December 16, 2010
Ischemia, MMPs and Myelin loss
December 16, 2010 at 10:47am
Continuing the exploration of the "auto-immune" reaction of the body in situations of slow blood flow, oxidative stress and lowered oxygen levels in the brain--we learn that myelin breakdown is not unique to MS. It happens in dementia, Alzheimer's, ischemic stroke, carbon monoxide poisoning and cerebrovascular disease.
There is recent research on myelin loss in ischemia.
This paper studies how matrix metalloproteinases (MMPs) are involved in this process--
MMPs: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis.
Multiple MMPs are elevated in human neurologic diseases. In the setting of MS, it has been shown that serum MMP-9 levels are increased in patients with clinically isolated syndrome (CIS) compared with normal control subjects and are further elevated in patients with clinically definite MS (CDMS) compared with patients with CIS. In addition, serum MMP levels increase markedly between onset of neurologic symptoms and development of CDMS, whereas levels remain unchanged in subjects with CIS who do not develop CDMS. Other studies have documented elevations of MMP-9 and other MMPs in the serum, CSF, and brain of patients with MS compared with controls.
Divergent role for MMP-2 in myelin breakdown and oligodendrocyte death following transient global ischemia.
Walker EJ, Rosenberg GA.
Departments of Neurology, Neurosciences, and Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
Transient global ischemia causes delayed white matter injury to the brain with oligodendrocyte (OLG) death and myelin breakdown. There is increasing evidence that hypoxia may be involved in several diseases of the white matter, including multiple sclerosis, vascular dementia, and ischemia.
Matrix metalloproteinases (MMPs) are increased in rat and mouse models of hypoxic hypoperfusion and have been associated with OLG death. However, whether the MMPs act on myelin or OLGs remains unresolved. We hypothesized that delayed expression of MMPs caused OLG death and myelin breakdown. To test the hypothesis, adult mice underwent hypoxic hypoperfusion with transient bilateral occlusion of the carotid arteries. After 3 days of reperfusion, ischemic white matter had increased reactivity of astrocytes and microglia, MMP-2 localization in astrocytes, and increased protein expression and activity of MMP-2. In addition, there was a significant loss of myelin basic protein (MBP) by Western blot and caspase-3- mediated OLG death. Treatment with the broad-spectrum MMP inhibitor, BB-94, significantly decreased astrocyte reactivity and MMP-2 activity. More importantly, it reduced MBP breakdown. However, MMP inhibition had no effect on OLG loss. Our results implicate MMPs released by reactive astrocytes in delayed myelin degradation, while OLG death occurs by an MMP-independent mechanism. We propose that MMP-mediated myelin loss is important in hypoxic injury to the white matter.