Molecular neurobiology
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Molecular neurobiology · Dec 2018
ReviewExosomes in Acquired Neurological Disorders: New Insights into Pathophysiology and Treatment.
Exosomes are endogenous nanovesicles that play critical roles in intercellular signaling by conveying functional genetic information and proteins between cells. Exosomes readily cross the blood-brain barrier and have promise as therapeutic delivery vehicles that have the potential to specifically deliver molecules to the central nervous system (CNS). This unique feature also makes exosomes attractive as biomarkers in diagnostics, prognostics, and therapeutics in the context of multiple significant public health conditions, including acquired neurological disorders. ⋯ In total, ten research articles were identified that examined exosomes in the context of TBI, SCI, or stroke; these manuscripts were reviewed and synthesized to further understand the current role of exosomes in the context of acquired neurological disorders. Of the ten published studies, four focused exclusively on TBI, one on both TBI and SCI, and five on ischemic stroke; notably, eight of the ten studies were limited to pre-clinical samples. The present review is the first to discuss the current body of knowledge surrounding the role of exosomes in the pathophysiology, diagnosis, and prognosis, as well as promising therapeutic strategies in TBI, SCI, and stroke research.
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Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. ⋯ In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.
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Phantom limb pain (PLP) is a chronic neuropathic pain occurring in 45-85% of patients who undergo major amputations of the upper and lower extremities. Chronic pain is physically and mentally debilitating, affecting an individual's potential for self-care and the performance of daily living activities essential for personal and economic independence. In addition, chronic pain may lead to depression and feelings of hopelessness. ⋯ However, it is not clear how the changes in neuronal properties in these different locations affect neuropathic pain. Is pain initiated by one set of post-amputation changes while the pain is maintained by another set of changes? If one set of amputation-induced changes, such as those of peripheral axons, are reverted to normal, is the chronic pain reduced or eliminated, while reversing another set of neuronal changes and neuronal circuits to normal do not reduce or eliminate the pain? Or, must all the amputation-induced changes be reverted to normal for pain to be eliminated? While this review examines the mechanisms underlying the induction or maintenance of PLP, it is beyond its scope to examine the mechanisms that may permanently reduce or eliminate neuropathic pain. This paper is the first of two reviews in this journal and deals with the causes of chronic PLP development and maintenance, while the second review examines potential mechanisms that may be responsible for promoting the capacity to coping with PLP by reducing or eliminating it.
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Prion diseases in humans are neurodegenerative diseases which are caused by an accumulation of abnormal, misfolded cellular prion protein known as scrapie prion protein (PrPSc). Genetic, acquired, or spontaneous (sporadic) forms are known. Pathogenic mutations in the human prion protein gene (PRNP) have been identified in 10-15 % of CJD patients. ⋯ Some non-coding mutations and new mutations in the PrP gene have been identified without clear evidence for their pathogenic significance. In the present review, we provide an updated overview of PRNP mutations, which have been documented in the literature until now, describe the change in the DNA, the family history, the pathogenicity, and the number of described cases, which has not been published in this complexity before. We also provide a description of each genetic prion disease type, present characteristic histopathological features, and the PrPSc isoform expression pattern of various familial/genetic prion diseases.
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Molecular neurobiology · Apr 2017
ReviewAnalysis of the Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Traumatic Brain and Spinal Cord Injury: Insight into Recent Advances in Actions of Neurochemokine Agents.
CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its biological properties through interaction with one dedicated CX3CR1 receptor which belongs to a family of G protein-coupled receptors (GPCR). ⋯ Recent evidence has implicated the role of the CX3CL1/CX3CR1 axis in neuroinflammatory processes occurring after CNS injuries. The importance of the CX3CL1/CX3CR1 axis in the pathophysiology of TBI and SCI in the context of systemic and direct local immune response is still under investigation. This paper, based on a review of the literature, updates and summarizes the current knowledge about CX3CL1/CX3CR1 axis involvement in TBI and SCI pathogenesis, indicating possible molecular and cellular mechanisms with a potential target for therapeutic intervention.