Browsing by Author "Bushell, T"
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Publication Immune Responses in Neurodegenerative Diseases(Kathmandu University, 2014) Shrestha, R; Shakya, Shrestha S; Millington, O; Brewer, J; Bushell, TABSTRACT Neurodegenerative disease is a progressive loss of neurons from central nervous system and has a huge impact on health care system. Various causes have been proposed of which inflammation has been suggested to be a probable key factor in the most of such conditions. The involvement of immune cells including lymphocytes in such diseased condition of the CNS supports this notion. The effective therapy for these diseases has been sought for more than a half century but still lacking such therapy. On such basis this review article has mainly focussed on evidence of the involvement of immune cells in various neurodegenerative diseases including Alzheimer’s disease, Parkinson’s diseases and Multiple sclerosis and suggests a possible therapy of such diseased conditions of the CNS by the modulation of immune system. KEYWORDS Alzheimer’s disease, lymphocytes, multiple sclerosis, neurodegenerative diseases, parkinson’s disease, stroke, t cellsPublication Is Central Nervous System an Immune-Privileged Site?(Kathmandu University, 2013) Shrestha, R; Millington, O; Brewer, J; Bushell, TABSTRACT The central nervous system (CNS) was once considered to be an immune-privileged area. However, increasing evidence shows that the central nervous system is not an immune-privileged but is an active surveillance site. There is a bi-directional communication between the central nervous system and immune system. Normally, immune cells migrate into the central nervous system microenvironment through choroid plexus and interact with the central nervous system resident cells through either through neuromediators or immunomediators. This finding has led to a significant interest in neuroimmunological interactions and investigation onto the role of the immune system in the pathology of various neurological disorders and examine whether it can be targeted to produce novel therapeutic strategies. KEYWORDS Central nervous system, immune-privileged, blood-brain barrier, immune cells and lymphocytesPublication Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration(Kathmandu University, 2013) Shrestha, R; Millington, O; Brewer, J; Bushell, TABSTRACT Background Neurodegenerative disease is a progressive loss of neurons from the central nervous system (CNS). Various conditions have been implicated for such conditions including ageing, inflammation, stress and genetic predisposition. Recently, studies have linked neurodegeneration with inflammation. Some studies have suggested the harmful effect of immune response while others have argued its neuroprotective role in neurodegeneration of the CNS. However, the precise role of inflammation and immune cells in such condition is still not clear. Objective To investigate the role of lymphocytes in neurodegeneration of the CNS and determine the underlying mechanism. Method We have used 4-7 days old mouse pups (C57Bl6) to prepare organotypic slice cultures which were cultured for 13-15 days prior to experiment. To induced cell death kainic acid was used and considered as an in vitro model for neurodegeneration. Lymphocytes were obtained from peripheral lymph nodes of 5-10 weeks old adult mouse which were used in the current study. Propidium iodide was used as a fluorescent dye to determine cell death in brain slice cultures. Result Lymphocytes do not induce cell death in slice cultures in the absence of any toxic insult whereas, after applying toxic insult to the slice cultures using kainic acid, lymphocytes show neuroprotection against such insult. Similarly, purified non- activated and purified activated T cells along with T cells depleted lymphocyte preparation also exhibit neuroprotection against kainic acid-induced cell death. We further, have demonstrated that the observed neuroprotection is contact- independent and soluble mediators released from lymphocytes are responsible for the observed neuroprotection. Moreover, our study has revealed that soluble mediators exhibiting neuroprotection act via astrocytes. Conclusion Lymphocyte preparations are neuroprotective and the observed neuroprotection is contact-independent. Soluble mediators released from lymphocytes are responsible for the observed neuroprotection. KEY WORDS Astrocytes, lymphocytes, neurodegeneration, neuroprotection, t cells