The majority of people with stroke regard walking in their community as very important (Lord et al 2004). Walking in the community is limited by slow walking speeds and poor walking capacity (Lord et al 2004; Patterson et al 2007). Slow walking speeds and poor walking capacity are identified sequela in people with stroke (Hill et al 1997). By the end of rehabilitation approximately 80% of people with stroke achieve independent walking (Dean & Mackay 1992; Hill et al 1997). However, less than 10 percent are able to easily walk in their community (Hill et al 1997). Optimal motor learning requires task-specific practice (Carr & Shepherd 2003). Treadmills offer the opportunity for repetitive practice of complete gait cycles (Shepherd & Carr 1999), potentially providing greater intensity and longer duration walking practice than usual physiotherapy rehabilitation. Recently there has been some suggestion that high-intensity interventions may improve walking in people with stroke (Moseley et al 2005). Low levels of cardiorespiratory fitness in people with stroke have been shown to impact on walking, in particular walking capacity (Kelly et al 2003). Treadmills, commonly used to retrain cardiorespiratory fitness in the healthy population, have been used to implement high-intensity interventions, improving cardiorespiratory fitness in people with chronic stroke (Macko et al 2005). Therefore it is possible that exercise aimed at improving cardiorespiratory fitness may improve walking in people with stroke. The aim of these four studies was to investigate in those following stroke if walking on a treadmill at high-intensity during inpatient rehabilitation could improve walking capacity without compromising pattern and quality. The first study determined, in an Australian setting, the duration and intensity of usual physiotherapy rehabilitation. Study 2 compared walking pattern immediately following overground and treadmill walking practice at the same intensity. Study 3 examined the effect of treadmill walking at intensities high enough to influence cardiorespiratory fitness on walking pattern and quality. The final study, investigated the feasibility of implementing a high-intensity treadmill intervention in addition to usual physiotherapy rehabilitation in people following stroke able to walk undergoing inpatient rehabilitation. Intensity in all studies was calculated using heart rate reserve or the Karvonen method. Heart rate is a valid, accurate and stable indicator of exercise intensity due to its relatively linear relationship with oxygen consumption (ACSM 2006). For those people taking beta-blocker medication, the heart rate-lowering effect of this type of medication was accommodated. A target intensity of 40% heart rate reserve was used; as this is the minimum required improve cardiorespiratory fitness (ACSM 2006). Walking pattern and quality were measured in Studies 2-4. Walking pattern was measured by linear kinematics using GAITRite (CIR Systems, Clifton, NJ, USA) and angular kinematics using a 2-dimensional webcam application. Walking quality was determined by observation of the webcam footage and scored using the Rivermead Visual Gait Assessment, Wisconsin Gait Scale and a vertical visual analogue scale by blinded assessor. The first study found that people with stroke spent an average of 21 (SD 11) minutes participating in standing and walking activities that are associated with reaching the target intensity during physiotherapy rehabilitation. Those who could walk spent longer in these activities (25 minutes, SD 12) compared to those would couldn’t walk (17 minutes, SD 9). However, the intensity of these activities was low; walkers reached a maximum of 30% heart rate reserve and non-walkers reached 35% heart rate reserve. Using the treadmill as a mode of task-specific physiotherapy rehabilitation, the second study in this thesis found that walking pattern was similar following 10 minutes of treadmill and overground walking practice at the same intensity. The third study found that during walking on the treadmill at intensities high enough to influence cardiorespiratory fitness (up to 60% heart rate reserve), many of the linear and angular kinematic parameters moved closer to a more normal pattern and walking quality was not compromised. The final study in this thesis, a randomised controlled trial, found that a 6-week high-intensity treadmill walking intervention was feasible in people with stroke able to walk who were undergoing rehabilitation. Participants attended 89% of the treadmill sessions, reaching an average duration of more than 20 minutes and an intensity of 40% heart rate reserve after two weeks. The intervention also appeared effective with significant improvements in walking speed and capacity following the treadmill walking intervention. Improvements in walking speed were maintained at 3 months. In summary, these studies found that usual physiotherapy in people with stroke was of low intensity. In addition, it was found that treadmill walking was safe and feasible as a means of increasing the intensity of physiotherapy rehabilitation, without compromising walking quality and pattern. Therefore, it may be possible to improve walking in people with stroke using high-intensity treadmill walking.

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Stroke is a pathological condition that causes extensive brain damage. During ischemic stroke, an excess of the excitatory neurotransmitter glutamate exerts many deleterious effects, which leads to cellular damage and cell death, a phenomenon appropriately termed excitotoxicity. Among the events triggered is the activation of the enzyme calpain, a protease whose action is dependent on the intracellular concentration of calcium, which is known to be elevated during excitotoxicity. In this thesis, I hypothesize that neuroprotective drugs can be better accumulated into stroke-affected regions by utilizing the actions of calpain. The extent of calpain activation was first investigated, and it was found to increase over time in both in vitro and in vivo models of stroke. Different amino acid sequences recognized and cleaved by calpain were then incorporated into the neuroprotective Tat-GluR2/3Y peptide. Although in vivo detection of modified Tat-GluR2/3Y peptides was unsuccessful due to technical difficulties, the accumulation of the therapeutic 3Y peptide fragments in neurons under excitotoxic conditions in vitro was found to increase with the CP-3 peptide, a peptide that is a modified version of the Tat-GluR2/3Y, with a sequence cleavable by calpain from the protein Collapsin Response Mediator Protein-3 (CRMP-3). These results suggest that it is possible to concentrate therapeutic agents into stroke-affected neurons, and this may translate into enhanced neuroprotective properties in both in vitro and in vivo animal stroke models.

SAMMANFATTNING Bakgrund: Stroke är ett samlingsnamn för både infarkter och blödningar som drabbar hjärnan. Stroke är bland de vanligaste sjukdomarna som drabbar den svenska befolkningen. Stroke är inte bara en sjukdom som drabbar den som insjuknar utan påverkar hela familjen. Syfte: Syftet med vår systematiska litteraturstudie var att belysa anhörigas upplevelse av när en närstående drabbats av en stroke och överlevt. Metod: Systematisk litteraturstudie av både kvalitativa och kvantitativa studier som analyserades utifrån en kvalitativ innehållsanalys. Resultat: Anhörigas livssituation och livskvalité förändrades då en närstående drabbades av stroke. Deras eget liv åsidosattes för den sjuke och vardagen förändrades. Den nya livssituationen medförde en känsla av stress, otillräcklighet, börda och oro. Funktionsnedsättningen hos den strokedrabbade påverkade anhörigas syn på framtiden. Vid förekomsten av kognitiv svikt upplevdes framtiden som mer osäker. Copingstrategier som egentid, socialt nätverk och hjälp med avlastning uppkom för att underlätta situationen. Makorna upplevde en sämre livskvalitet jämfört med makarna. Slutsats: Vid en stroke förändrades livet för både den strokedrabbade och anhöriga. För att kunna ge en god vård och ett gott bemötande, till både patienten som anhöriga, krävs förståelse för anhörigas upplevelse av att vårda en närstående. Med denna förståelse kan bättre information och stöd ges från vårdens sida. Nyckelord: Stroke, anhörig, livskvalité, framtidssyn, upplevelse

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Stroke är en av våra vanligaste folksjukdomar. Många strokedrabbade med fysiska och/eller psykiska funktionsnedsättningar vårdas i hemmet av anhörigvårdare. Syftet med denna litteraturstudie var att belysa anhörigas erfarenheter av att vårda strokedrabbade med fysiska och psykiska funktionsnedsättningar i hemmet. Metoden som användes var systematisk litteraturstudie. Studien grundades på 16 artiklar som hämtades från databaserna Cinahl, Pubmed och ELIN. Resultatet visade att många anhörigvårdare kände sig oförberedda på rollen som vårdare på grund av att insjuknandet i stroke ofta sker akut. Livssituationen förändrades drastiskt och detta innebär en stor påfrestning på det dagliga livet. Förändringarna i livssituationen medförde ett stort behov av olika former av stöd. Socialt/emotionellt och informativt stöd var avgörande för den fortsatta vården i hemmet, och var viktigt för att förebygga ohälsa hos anhörigvårdare. Bristande stöd kunde påverka livssituationen och därmed hälsan på ett negativt sätt. Anhörigvårdare var trots upplevda svårigheter tacksamma för att den strokedrabbade levde och kunde bo hemma. Slutsats: forskning om anhörigas erfarenheter av att vårda är viktiga för sjuksköterskors samarbete med anhörigvårdare till strokedrabbade.

Stroke is the third most common leading cause of death worldwide and is a major cause of serious long-term disability among adults. Platelet activation and it¡¦s interaction with leukocytes plays an important role in the pathophysiology of ischemic stroke. Anti-platelet drugs are widely used for secondary prevention after cerebral ischemia of non-cardioembolic origin and different anti-platelet drugs exert different pharmacologic effects on platelets. Several stimulations cause elevation of cytosolic Ca2+ level ([Ca2+]i), activating the secondary messenger in the platelet, and then leading to platelet activation. The majority of damage following acute stroke does not occur immediately, but rather develops gradually over the course of the following hours. Leukocytes are believed to liberate inflammatory cytokines and other neurotoxins in the ischemic brain and to promote microvascular occlusion through platelet-leukocyte-endothelium interactions in the ischemic penumbra. In this thesis, we tested the serial changes of platelet [Ca2+]i movement in patients after acute ischemic stroke. We evaluated platelet activation markers, leukocyte adhesion molecules and platelet-leukocyte interaction in patients with acute ischemic stroke. We also analyzed the relationship between these biomarkers and the clinical outcome. Furthermore, we compared the antiplatelet effect of aspirin and clopidogrel in patients after acute stroke Dysregulation of Ca2+ Movement in Platelets from Patients with Acute Ischemic Stroke Thirty-one patients with acute ischemic stroke and 27 at-risk controls were enrolled in this study. The platelet [Ca2+]i was measured using a fluorescent dye fura-2 after stimulation with arachidonic acid (AA), adenosine diphosphate (ADP), platelet-activation factor (PAF), and thrombin. The basal [Ca2+]i was higher in the stroke group than in the at-risk controls irrespective of the presence or absence of extracellular Ca2+. In the Ca2+-containing medium, both PAF and ADP, but not AA and thrombin, significantly increased the platelet [Ca2+]i in the stroke patients than in the at-risk controls. However, in the Ca2+-free medium, only PAF significantly increased the platelet [Ca2+]i in the stroke patients than in the at-risk controls. The basal [Ca2+]i and PAF-induced platelet [Ca2+]i rises were still higher in the stroke patients at the subacute stage than in the at-risk controls. Levels and Value of Platelet Activation Markers in Different Subtypes of Acute Non-Cardio-Embolic Ischemic Stroke Platelet activation markers (CD62P, CD63, and CD40L) and platelet-leukocyte interaction were measured by flow cytometry at different time points in 54 (32 small-vessel and 22 large-vessel diseases) acute ischemic stroke patients, 28 convalescent stroke patients (3 to 9 months after acute stroke), and 28 control subjects. Patients with ischemic stroke had significantly increased circulating CD62P, CD63, platelet-monocyte interaction, and platelet-lymphocyte interaction in the acute stage compared with the convalescent stage and control groups. Levels of CD62P and CD63 were significantly higher in the large-vessel disease group than in the small-vessel disease group, and differences in CD62P were significant even at one month. The CD40L level in the poor outcome group was significantly higher than that in the good outcome group. The Value of Leukocyte Adhesion Molecules in Patients after Ischemic Stroke We examined serially the change of PSGL-1, Mac-1, and LFA-1 expression on leukocytes by using flow cytometry at various time points in 65 acute ischemic stroke patients and 60 controls. PSGL-1 expression on neutrophils and monocytes was significantly higher from Day 1 to Day 90 after stroke as compared with control subjects. The expression of monocyte Mac-1, LFA-1, and neutrophil Mac-1 were more significantly increased on Day 1 and 7 after stroke as compared with the control subjects. Furthermore, the neutrophil PSGL-1 expression on admission was independently associated with early neurologic deterioration. Serial Changes in Platelet Activation Markers with Aspirin and Clopidogrel after Acute Ischemic Stroke We designed a prospectively randomized case-control study and 70 patients with non-cardioembolic stroke who were treated with either aspirin (100 mg/d) or clopidogrel (75 mg/d) after acute ischemic stroke were evaluated. Ischemic stroke patients had significantly increased circulating CD62P, CD63, and CD40L in the acute stage as compared to the control group. Levels of CD62P, CD63 and CD40L were more significantly reduced in the clopidogrel group than in the aspirin group in the first week after stroke. Furthermore, differences in CD62P and CD63 levels were significant even at one-month post-stroke. Conclusion Stroke patients have enhanced platelet activity and platelet-leukocyte interaction in acute and convalescent phase of ischemic stroke compared with controls. Large-vessel cerebral infarction elicits higher platelets activation than small-vessel infarction in the acute phase of stroke. The dysregulation of Ca2+ movement, through the PAF- and ADP- receptor mediated pathway, in platelets may persist up to the subacute stage of ischemic stroke. It is possible that clopidogrel, an ADP-receptor inhibitor, elicit stronger antiplatelet effect than aspirin in the acute and convalescent phases after ischemic stroke. Sustained leukocyte-endothelium interaction, as reflected by expression of Mac-1 and LFA-1 on circulating leukocytes, may cause substantial inflammatory reaction and lead to secondary injury of potentially salvageable neurons after cerebral infarction. Ischemic stroke patients presenting with a higher CD40L level on admission were associated with a 3-month poor outcome.

Thesis (MPhil) -- AUT University, 2009. / Includes bibliographical references. Also held in print (xiv, 156 leaves : charts. ; 30 cm.) in the Archive at the City Campus (T 616.810645 ROS)