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dc.contributor.advisorClarkson, Andrew
dc.contributor.authorWright, Timothy Edward
dc.date.available2016-04-06T21:39:43Z
dc.date.copyright2016
dc.identifier.citationWright, T. E. (2016). Effects of de-enrichment on post-stroke learning and microglial activation in mice (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/6352en
dc.identifier.urihttp://hdl.handle.net/10523/6352
dc.description.abstractStroke is a leading cause of death and lasting disability in adults. The extent of recovery is mediated in part by the patient’s environment both before and after stroke. Institutionalisation or loss of work, leisure activities or social contact constitutes a loss of enrichment and impairs recovery, as well as increasing the risk of depression and anxiety. Previous animal studies have not examined the effect of a period of pre-stroke enrichment followed by post-stroke loss of enrichment. Therefore, we aimed to model this situation using three different levels of enrichment after stroke: Continued ‘normal’ environmental enrichment (EE), de-enrichment (DE), or enhanced enrichment (EEE). Further, we aimed to assess the possible interaction of medial prefrontal cortex (mPFC) lesions and changes in environment and stress on recognition learning and microglial activation, as a marker for inflammation. Adult male C57BL/6J mice were housed for three months in an enriched environment prior to receiving photothrombotic lesions to the mPFC. Immediately after stroke, animals were placed into one of the three environmental conditions: EE, DE, or EEE. Behavioural testing was carried out at one and four weeks post-stroke and included grid walking and cylinder tests to measure motor skills, open field to measure activity levels and anxiety, elevated plus maze and light-dark box to measure anxiety, and novel object and object location recognition to measure learning and memory. Following testing, animals were sacrificed and their brains analysed for stroke volume and secondary degeneration through microglial activation. DE animals had smaller lesion volumes one week after stroke. Stroke and housing conditions had mixed effects on activity levels and anxiety, and had no effect on object memory. Similar to what we have shown previously, stroke EE and stroke EEE groups showed delayed spatial memory impairment at four weeks. Stroke decreased IBA1-positive microglial staining in several brain regions, except for some dense cores seen in the thalamus and median eminence. EE and EEE reduced staining in stroke animals in several areas, including the thalamus and median eminence, which was associated with spatial memory impairment, and may indicate secondary neuronal degeneration in spatial memory circuits. Interestingly, the stroke DE group showed no impairment in spatial memory seen at 4-weeks post-stroke. In addition, these animals also showed no decrease in IBA1 staining in the thalamus, indicating that IBA1 activation may be mitigating the secondary neuronal cell loss associated with the spatial memory impairments. In human patients secondary neuronal loss is common and can lead to delayed cognitive decline. This loss may contribute to post-stroke depression and anxiety. The negative effects of early enrichment may be caused by an increase in stress in the enrichment groups, combined with disruption to the hypothalamic-pituitary-adrenal (HPA) axis caused by mPFC damage. These results may indicate that de-enrichment is protective early after stroke, and that treatment is best delayed for some hours or days to maximise recovery and minimise delayed impairments.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectStroke
dc.subjectC57BL/6J
dc.subjectmice
dc.subjectphotothrombosis
dc.subjectenvironmental enrichment
dc.subjectmedial prefrontal cortex
dc.subjectde-enrichment
dc.subjectmicroglia
dc.subjectIBA1
dc.subjectgrid-walking
dc.subjectcylinder
dc.subjectopen field
dc.subjectnovel object
dc.subjectobject recognition
dc.subjectelevated plus maze
dc.subjectlight-dark box
dc.subjectmotor skills
dc.subjectanxiety
dc.subjectdepression
dc.subjectlesion volume
dc.subjectlearning
dc.subjectmemory
dc.subjectpost-stroke
dc.subjectdelayed spatial memory impairment
dc.subjectthalamus
dc.subjectmedian emminence
dc.subjectsecondary neuronal loss
dc.subjectdelayed cognitive decline
dc.subjectstress
dc.subjecthypothalamic-pituitary-adrenal
dc.subjectHPA
dc.titleEffects of de-enrichment on post-stroke learning and microglial activation in mice
dc.typeThesis
dc.date.updated2016-04-06T09:16:01Z
dc.language.rfc3066en
thesis.degree.disciplineAnatomy
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.openaccessOpen
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