Browsing by Subject "multiple sclerosis"

Now showing 1 - 4 of 4
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    Identification of N-benzyltetrahydroisoquinolines as novel anti-neuroinflammatory agents
    (Elsevier, 2018-11) Gabet, Brian; Kuo, Ping-Chang; Fuentes, Steven; Patel, Yamini; Adow, Ahmed; Alsakka, Mary; Avila, Paula; Beam, Teri; Yen, Jui-Hung; Brown, Dennis A.; Medicine, School of Medicine
    A series of simplified berberine analogs was designed, synthesized, and evaluated for anti-inflammatory activity. SAR studies identified N-benzyltetrahydroisoquinoline 7d as a potent berberine analog. 7d suppressed LPS-induced inflammatory cytokine levels in both BV2 cells and primary microglia. Taken together, our results suggest that simplified BB analogs have therapeutic potential as a novel class of anti-neuroinflammatory agents.
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    New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage
    (MDPI, 2013-10-09) Tully, Melissa; Shi, Riyi; Medicine, School of Medicine
    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS) scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE) mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.
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    Optogenetics and its application in neural degeneration and regeneration
    (Wolters Kluwer, 2017-08) Ordaz, Josue D.; Wu, Wei; Xu, Xiao-Ming; Neurological Surgery, School of Medicine
    Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer’s disease and Parkinson’s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.
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    Should Patients with Optic Neuritis Be Treated with Steroids?
    (Lippincott Williams & Wilkins, 2015) Mackay, Devin D.; Department of Ophthalmology, IU School of Medicine
    Purpose of review: Optic neuritis is the most common cause of optic neuropathy in young adults. High-dose intravenous corticosteroids (IVCS) were established as the standard of treatment for acute optic neuritis via the Optic Neuritis Treatment Trial (ONTT), with its first findings published more than 20 years ago. Subsequent studies have further clarified the role of corticosteroids in the treatment of acute optic neuritis. Recent findings: Recent clinical research has confirmed existing knowledge of the efficacy and limitations of corticosteroids in the treatment of optic neuritis. Recent studies have examined the role of race, route of administration and combination of IVCS with other therapies. Current evidence continues to support high-dose IVCS as the cornerstone of treatment of acute optic neuritis. Summary: High-dose IVCS are effective in hastening visual recovery in acute typical optic neuritis, but do not affect the final visual outcome. In optic neuritis patients, IVCS may delay progression to clinically definite multiple sclerosis (CDMS) at 2 years, but not at 5 or 10 years. It is reasonable to recommend high-dose IVCS for acute optic neuritis patients with significant vision loss, severe pain and/or white matter lesions on brain MRI in whom the potential for benefit outweighs the risks.