One of the most common risk factors for stroke is diabetes. Diabetics are 2 to 4 times more likely to have a stroke and are also significantly more likely to show poor functional recovery. In order to determine why diabetes is associated with poor stroke recovery, we tested the hypotheses that diabetes either exacerbates initial stroke damage, or inhibits neuronal circuit plasticity in surviving brain regions that is crucial for successful recovery. Type 1 diabetes was chemically induced in mice four weeks before receiving a targeted photothrombotic stroke in the right forelimb somatosensory cortex to model a chronic diabetic condition. Following stroke, a subset of diabetic mice were treated with insulin to determine if controlling blood glucose levels could improve stroke recovery. Consistent with previous studies, one behavioural test revealed a progressive improvement in sensory function of the forepaw in non-diabetic mice after stroke. By contrast, diabetic mice treated with and without insulin showed persistent deficits in sensori-motor forepaw function. To determine whether these different patterns of stroke recovery correlated with changes in functional brain activation, forepaw evoked responses in the somatosensory cortex were imaged using voltage sensitive dyes at 1 and 14 weeks after stroke. In both diabetic and non-diabetic mice that did not have a stroke, brief mechanical stimulation of the forepaw evoked a robust and near simultaneous depolarization in the primary (FLS1) and secondary somatosensory (FLS2) cortex. One week after stroke, forepaw-evoked responses had not been remapped in the peri-infarct cortex in both diabetic and non-diabetic mice. Fourteen weeks after stroke, forepaw evoked responses in non-diabetic mice re-emerged in the peri-infarct cortex whereas diabetic mice showed very little activation, reminiscent of the 1 week recovery group. Moreover, controlling hyperglycemia using insulin therapy failed to restore sensory evoked responses in the peri-infarct cortex. In addition to these differences in peri-infarct responsiveness, we discovered that stroke was associated with increased responsiveness in FLS2 of non-diabetic, but not diabetic or insulin treated mice. To determine the importance of FLS2 in stroke recovery, we silenced the FLS2 cortex and found that it re-instated behavioural impairments in stroke recovered mice, significantly more so than naïve mice that still had a functioning FLS1. Collectively, these results indicate that both diabetes and the secondary somatosensory cortex play an important role in determining the extent of functional recovery after ischemic cortical stroke. Furthermore, the fact that insulin therapy after stroke did not normalize functional recovery, suggests that prolonged hyperglycemia (before stroke) may induce pathological changes in the brain’s circulation or nervous system that cannot be easily reversed. / Graduate

Background: Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. Methods: We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055. Results: We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upperextremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Conclusion: Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Following a stroke, normal usage of the impaired limb guides spontaneous recovery across many months or even years; however, recovery is rarely complete. Pre-clinical tools are needed to investigate stroke-induced cortical reorganization over long periods. This thesis aims to characterize stroke impairment and spontaneous recovery in parallel with a battery of behaviour tasks in a mouse model of focal stroke. Young adult Thy1-ChR2 mice were implanted with a transcranial window over the intact skull permitting cortex visualization and enabling longitudinal assessments with light-based motor mapping and intrinsic signal optical imaging. Furthermore, mice were tested on sensorimotor behavioural tasks in parallel to the mapping experiments. These experiments allowed for the quantification of impairments in the sensorimotor cortex and forelimb function while identifying regions within the sensorimotor cortex that show re-mapping associated with behavioural recovery. Following primary motor cortex-stroke induction, both sensory and motor map impairments occurred. Sensory map transient impairments recovered within the same atlas-defined regions two weeks after a primary motor cortex stroke as identified by intrinsic signal optical imaging. In contrast, motor forelimb recovery was observed four weeks after the stroke in the peri-infarct region, the supplemental motor cortex, and the contralesional motor cortex. This recovery was identified through a combination of analyses, including changes in the mapped area and the amplitude of evoked forelimb movements using light-based motor mapping. Behavioural recovery occurred four to six weeks post-stroke, depending on the sensitivity of the task in forelimb impairment. Additionally, the contralesional hemisphere and forelimb did not show impairment acutely but evoked forelimb amplitude was significantly increased by post-stroke week four for both forelimbs. As the first study to conduct within-animal longitudinal spontaneous recovery sensory and motor map experiments using bilateral forelimb and hemispheric representations, we show that 1) photothrombotic stroke impacts both forelimb representations pertained within the ipsilesional hemisphere in LBMM experiments, 2) recovery of the impaired forelimb occurs ipsilesionally and contralesionally and, 3) impairments from stroke observed through motor mapping are functionally relevant and precede behavioural recovery ranging from zero to two or more weeks depending on the motor cortex's involvement in the behavioural task.

Stroke recovery is complex and poorly understood. As a legacy of pervasive pessimism in the face of limited treatment, it is conceptualised and researched from biomedical and psychosocial perspectives that address impairment, problems of performance, quality of life, burden and disruption. Little stroke research is conducted once professional input has ceased, and yet considerable change occurs after this period with evidence that post-stroke wellbeing is independent of impairment and function -- many people do well in the face of poor prognoses, while others remain miserable despite 'good recovery'. Current advances in acute stroke management are generating increasing optimism, but lack of understanding about individuals' post-stroke experiences and long-term outcomes continues. While it is recognised that the impact of stroke on the lives of survivors and families is profound, rehabilitation focuses on recovery as task achievement and measured functional outcomes. For many survivors and their families 'recovery' is contested, ambiguous and extended. For some, it becomes a lifetime marathon because stroke represents an assault, not only to the body, but to the self and the lifeworld -- it is a 'life' event. This narrative inquiry into life after stroke explores recovery as a process taking place over time and conceptualised as a life transition. The work is grounded in narrative theory with the concept of transition providing the lens and focus for the research, its processes and analyses. Individuals' stories remain intact enabling evocation of diverse stroke meanings and the mapping of individual experience. Bringing these whole stories into conversation with each other elucidates post-stroke transition which is interpreted in light of theories of response to traumatic loss and informed by narrative theory. The thesis presents stories of trauma, loss and grief, situated in past lives and selves where assumptions about selves and future lives are shattered. The future makes no sense in terms of participants' past and present lives; life plots are lost and stroke therefore represents 'lost futures'. Stories of moving on to new lives are focused on being and doing in the present and have an expectant view of life. Although mindful of past lives and enduring losses, survivors actively engage in processes to reconfigure their lives with hope for a meaningful future. Transition is interpreted as 'reconfiguring the future'. The life tasks of reconfiguration are embedded in dynamic models of traumatic loss where grief is conceptualised as recursive movement between loss and meaning reconstruction evident in narratives that slowly move towards wellbeing. Despite broad recognition that loss and grief are part of the stroke experience, they are rarely addressed; where attention is paid it is likely embedded in explanatory models of staged response that oversimplify human experience. This thesis offers a new framework. It represents a fresh interpretation that highlights the ongoing traumatic impact of stroke. The post-stroke journeys of survivors and families are affected by individual circumstances and meanings. Although their stories are permeated with loss, many people move forward towards lives worth living. This interpretation suggests ways of reconfiguring lives in the face of devastation and ongoing traumatic loss. The work identifies a complex interaction of individual, emotional and social factors contributing to transitions to wellbeing following stroke and thus adds to a prospective vision of post-stroke life that can inform rehabilitation, discharge and stroke support strategies. Post-stroke transition will be enhanced when we use narrative framing and understanding to guide rehabilitative practice that uses meaning-centred models to prepare survivors and their families for a return to the lifeworld. / Thesis (PhD)--University of South Australia, 2009

Stroke recovery is complex and poorly understood. As a legacy of pervasive pessimism in the face of limited treatment, it is conceptualised and researched from biomedical and psychosocial perspectives that address impairment, problems of performance, quality of life, burden and disruption. Little stroke research is conducted once professional input has ceased, and yet considerable change occurs after this period with evidence that post-stroke wellbeing is independent of impairment and function -- many people do well in the face of poor prognoses, while others remain miserable despite 'good recovery'. Current advances in acute stroke management are generating increasing optimism, but lack of understanding about individuals' post-stroke experiences and long-term outcomes continues. While it is recognised that the impact of stroke on the lives of survivors and families is profound, rehabilitation focuses on recovery as task achievement and measured functional outcomes. For many survivors and their families 'recovery' is contested, ambiguous and extended. For some, it becomes a lifetime marathon because stroke represents an assault, not only to the body, but to the self and the lifeworld -- it is a 'life' event. This narrative inquiry into life after stroke explores recovery as a process taking place over time and conceptualised as a life transition. The work is grounded in narrative theory with the concept of transition providing the lens and focus for the research, its processes and analyses. Individuals' stories remain intact enabling evocation of diverse stroke meanings and the mapping of individual experience. Bringing these whole stories into conversation with each other elucidates post-stroke transition which is interpreted in light of theories of response to traumatic loss and informed by narrative theory. The thesis presents stories of trauma, loss and grief, situated in past lives and selves where assumptions about selves and future lives are shattered. The future makes no sense in terms of participants' past and present lives; life plots are lost and stroke therefore represents 'lost futures'. Stories of moving on to new lives are focused on being and doing in the present and have an expectant view of life. Although mindful of past lives and enduring losses, survivors actively engage in processes to reconfigure their lives with hope for a meaningful future. Transition is interpreted as 'reconfiguring the future'. The life tasks of reconfiguration are embedded in dynamic models of traumatic loss where grief is conceptualised as recursive movement between loss and meaning reconstruction evident in narratives that slowly move towards wellbeing. Despite broad recognition that loss and grief are part of the stroke experience, they are rarely addressed; where attention is paid it is likely embedded in explanatory models of staged response that oversimplify human experience. This thesis offers a new framework. It represents a fresh interpretation that highlights the ongoing traumatic impact of stroke. The post-stroke journeys of survivors and families are affected by individual circumstances and meanings. Although their stories are permeated with loss, many people move forward towards lives worth living. This interpretation suggests ways of reconfiguring lives in the face of devastation and ongoing traumatic loss. The work identifies a complex interaction of individual, emotional and social factors contributing to transitions to wellbeing following stroke and thus adds to a prospective vision of post-stroke life that can inform rehabilitation, discharge and stroke support strategies. Post-stroke transition will be enhanced when we use narrative framing and understanding to guide rehabilitative practice that uses meaning-centred models to prepare survivors and their families for a return to the lifeworld. / Thesis (PhD)--University of South Australia, 2009

Stroke recovery is complex and poorly understood. As a legacy of pervasive pessimism in the face of limited treatment, it is conceptualised and researched from biomedical and psychosocial perspectives that address impairment, problems of performance, quality of life, burden and disruption. Little stroke research is conducted once professional input has ceased, and yet considerable change occurs after this period with evidence that post-stroke wellbeing is independent of impairment and function -- many people do well in the face of poor prognoses, while others remain miserable despite 'good recovery'. Current advances in acute stroke management are generating increasing optimism, but lack of understanding about individuals' post-stroke experiences and long-term outcomes continues. While it is recognised that the impact of stroke on the lives of survivors and families is profound, rehabilitation focuses on recovery as task achievement and measured functional outcomes. For many survivors and their families 'recovery' is contested, ambiguous and extended. For some, it becomes a lifetime marathon because stroke represents an assault, not only to the body, but to the self and the lifeworld -- it is a 'life' event. This narrative inquiry into life after stroke explores recovery as a process taking place over time and conceptualised as a life transition. The work is grounded in narrative theory with the concept of transition providing the lens and focus for the research, its processes and analyses. Individuals' stories remain intact enabling evocation of diverse stroke meanings and the mapping of individual experience. Bringing these whole stories into conversation with each other elucidates post-stroke transition which is interpreted in light of theories of response to traumatic loss and informed by narrative theory. The thesis presents stories of trauma, loss and grief, situated in past lives and selves where assumptions about selves and future lives are shattered. The future makes no sense in terms of participants' past and present lives; life plots are lost and stroke therefore represents 'lost futures'. Stories of moving on to new lives are focused on being and doing in the present and have an expectant view of life. Although mindful of past lives and enduring losses, survivors actively engage in processes to reconfigure their lives with hope for a meaningful future. Transition is interpreted as 'reconfiguring the future'. The life tasks of reconfiguration are embedded in dynamic models of traumatic loss where grief is conceptualised as recursive movement between loss and meaning reconstruction evident in narratives that slowly move towards wellbeing. Despite broad recognition that loss and grief are part of the stroke experience, they are rarely addressed; where attention is paid it is likely embedded in explanatory models of staged response that oversimplify human experience. This thesis offers a new framework. It represents a fresh interpretation that highlights the ongoing traumatic impact of stroke. The post-stroke journeys of survivors and families are affected by individual circumstances and meanings. Although their stories are permeated with loss, many people move forward towards lives worth living. This interpretation suggests ways of reconfiguring lives in the face of devastation and ongoing traumatic loss. The work identifies a complex interaction of individual, emotional and social factors contributing to transitions to wellbeing following stroke and thus adds to a prospective vision of post-stroke life that can inform rehabilitation, discharge and stroke support strategies. Post-stroke transition will be enhanced when we use narrative framing and understanding to guide rehabilitative practice that uses meaning-centred models to prepare survivors and their families for a return to the lifeworld. / Thesis (PhD)--University of South Australia, 2009