In MS, the connection of astrocyte "foot processes" with the glial limiting membrane is often gone (these foot processes form part of the blood-brain barrier .... perhaps MS is also a disease of astrocytes?
Increases in the T(1) of brain tissue, which give rise to dark or hypointense areas on T(1)-weighted images using magnetic resonance imaging (MRI), are common to a number of neuropathologies including multiple sclerosis (MS) and ischaemia
These findings suggest that an increase in T(1) relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion.
Early changes in T(1) may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS.
cheerleader wrote:This is the order Dr. Zamboni puts forth in his latest paper on cerebral bloodflow-the abstract and charts are in the research sticky-
1. CCSVI - chronic cerebrospinal venous insufficiency- a cerebral venous outflow abnormality caused by a congenital venous malformation
2. iron deposition into and oxygen deprivation of brain tissue
3. hypoxia and cellular death
4. activation of immune system
Shayk wrote:Just want to add that on the surface it seems the info about astrocytes and MS could be quite consistent with the info on CCSVI.
Per Hollie's (Accelerated Cure Project) 2009 Ectrims notes about Dr. Prineas' Charcot Award Lecture:
Is this the same order of events in "MS"? In "MS" are astrocytes destroyed or abnormal?MarkW wrote:[in Neuromyelitis Optica] Astrocytes are destroyed (they may come back but are abnormal), and myelin loss happens after the loss of astrocytes.
I have seen the term used a lot -- activated microglia. What are they? Good, bad, neither? What activates them?MarkW wrote:...He does not know why the oligos become apoptotic and whether the activated microglia are a cause or an effect of that.
Blood brain barrier (BBB) permeability is an early and prominent feature of inflammatory CNS conditions, including MS (13), viral encephalitis (14), and traumatic and hypoxic/ischemic injury (15). BBB disruption correlates with neurologic exacerbation, and MS patients with contrast-enhancing plaques are more likely to have irreversible pathology (13, 16). BBB breakdown leads to edema, metabolic imbalance, excitotoxicity, and ingress of factors that potentiate inflammation and inhibit repair (17–20) and facilitates infiltration of T and B lymphocytes, macrophages, and neutrophils (21). In diseases such as MS, current options to restrict relapse severity are limited, and patients may benefit from more selective agents (22).
Studies have identified astrocytes as regulators of BBB induction and maintenance (9–11) and have implicated astrogliosis, particularly induced by IL-1, as a driver of both BBB breakdown and repair (10, 12, 48). The mediators producing the effects of reactive astrocytes are incompletely characterized, and our data revealed VEGF-A as an important astrocyte-derived inducer of BBB disruption and pathology in vivo. Although VEGF-A–induced vascular permeability has previously been implicated in pathogenesis of disorders, including myocardial infarction, CNS hypoxia/reperfusion injury, and tumor growth and metastasis (49), and we and others have previously speculated on its role in BBB breakdown (12, 26), this study is the first to our knowledge to show the significance of astrocyte-derived VEGF-A in lesion pathogenesis and generation of clinical deficit in models of CNS inflammatory disease.
MarkW wrote:Prineas wrote:[in Neuromyelitis Optica] Astrocytes are destroyed (they may come back but are abnormal), and myelin loss happens after the loss of astrocytesIs this the same order of events in "MS"? In "MS" are astrocytes destroyed or abnormal?
....He does not know why the oligos become apoptotic and whether the activated microglia are a cause or an effect of that.1eye wrote:I have seen the term used a lot -- activated microglia. What are they? Good, bad, neither? What activates them?
Auto-antibody mediated astrocyte injury is implicated as a primary event in neuromyelitis optica (NMO) by biomarker, post-mortem and experimental studies that differentiate the condition from multiple sclerosis. .
Iron Efflux from Astrocytes Plays a Role in Remyelination
Katrin Schulz, Antje Kroner, and Samuel David+ Author Affiliations
Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Québec H3G 1A4, Canada
Author contributions: K.S. and S.D. designed research; K.S. and A.K. performed research; K.S. analyzed data; K.S. and S.D. wrote the paper.
How iron is delivered to the CNS for myelination is not well understood. We assessed whether astrocytes can provide iron to cells in the CNS for remyelination. To study this we generated a conditional deletion of the iron efflux transporter ferroportin (Fpn) in astrocytes, and induced focal demyelination in the mouse spinal cord dorsal column by microinjection of lysophosphatidylcholine (LPC). Remyelination assessed by electron microscopy was reduced in astrocyte-specific Fpn knock-out mice compared with wild-type controls, as was proliferation of oligodendrocyte precursor cells (OPCs). Cell culture work showed that lack of iron reduces the ability of microglia to express cytokines (TNF-α and IL-1β) involved in remyelination.
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