Intraspinal TLR4 activation promotes iron storage but does not protect neurons or oligodendrocytes from progressive iron-mediated damage.

Intraspinal TLR4 activation promotes iron storage but does not protect neurons or oligodendrocytes from progressive iron-mediated damage. Exp Neurol. 2017 Aug 26;: Authors: Goldstein EZ, Church JS, Pukos N, Gottipati M, Popovich PG, McTigue DM Abstract Iron is essential for basic cellular functions but in excess is highly toxic. For this reason, free iron and iron storage are controlled in the periphery by elaborate regulatory mechanisms. In contrast, iron regulation in the central nervous system (CNS) is not well defined. Given that excess iron is present after trauma, hemorrhagic stroke and neurodegeneration, understanding normal iron regulation and promoting iron uptake in CNS pathology is crucial. Peripherally, toll-like receptor 4 (TLR4) activation promotes iron sequestration by macrophages. Notably, iron-rich sites of CNS pathology typically contain TLR4 agonists, which may promote iron uptake. Indeed, our recent work showed impaired iron storage after acute spinal cord injury in mice with TLR4 deficiency. Here we used a reductionist model to ask if TLR4 activation in the CNS stimulates iron uptake and promotes neuroprotection from iron-induced toxicity. For this, we measured the ability of microglia/macrophages to sequester exogenous iron and prevent pathology with and without concomitant intraspinal TLR4 activation. Results show that, similar to the periphery, activating intraspinal TLR4 via focal LPS injection increased mRNA encoding iron uptake...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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Source: Current Neurovascular Research - Category: Neurology Authors: Tags: Curr Neurovasc Res Source Type: research
(University of California - San Diego) In a UC San Diego study, rats with spinal cord injuries experienced a three-fold increase in motor activity when treated with neural progenitor cells that had been pre-conditioned with a modified form of tPA, a drug commonly used to treat non-hemorrhagic stroke.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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Source: Neurocritical Care - Category: Neurology Source Type: research
Gangliosides are cell membrane components, most abundantly in the central nervous system where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled tria...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Shanshan Zhang1, Dongli Yuan2 and Ge Tan1* 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 2The Institute of Medical Information, Chongqing Medical University, Chongqing, China Primary systemic vasculitis can affect every structure in both the central and peripheral nervous system, causing varied neurological manifestations of neurological dysfunction. Early recognition of the underlying causes of the neurological symptoms can facilitate timely treatment and improve the prognosis. This review highlights the clinical manifestations of primary systemic vasc...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
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Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: SI on Prevention Strategies in the Critically Ill Source Type: research
Hypothermia is increasingly tested in several neurological conditions, such as neonatal encephalopathy, stroke, traumatic brain injury, subarachnoid hemorrhage, spinal cord injury, and neurological outcomes of...
Source: Journal of Neuroinflammation - Category: Neurology Authors: Tags: Short report Source Type: research
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Source: Behavioural Neurology - Category: Neurology Authors: Tags: Behav Neurol Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Journal of Spinal Cord Medicine - Category: Orthopaedics Tags: J Spinal Cord Med Source Type: research
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