Current therapeutic options for ischemic stroke are limited to tissue plasminogen activator and mechanical clot removal therapies. Diazoxide (DZ) is a mitochondrial ATP-sensitive potassium channel opener and is protective in models of brain ischemia, but the signaling pathways involved are unknown. The mammalian target of rapamycin (mTOR) is a master regulator of protein synthesis and is involved in protection against cerebral ischemia. The neuronal nitric oxide synthase (nNOS) pathway has also been shown to provide protection from ischemic insults. Additionally, mitochondrial respiratory status has not been investigated. I examined the role of the mTOR pathway, the nNOS pathway, and mitochondrial respiration in delayed DZ-induced preconditioning of neurons. I cultured rat primary cortical neurons and simulated ischemic stroke using oxygen-glucose deprivation (OGD) for 3 h followed by re-oxygenation. Viability, mitochondrial membrane potential, reactive oxygen species (ROS) measurements, and western blots were performed. The mTOR pathway was inhibited by rapamycin, Torin-1, and S6K targeted silencing RNA. The NOS pathway was inhibited by L-NAME. NO-donors SNP and DEANONOate (DEANO) were applied to rescue the effects of L-NAME. Mitochondrial oxygen consumption rate (OCR) was measured in intact neurons by serial injections of oligomycin, FCCP, and antimycin/rotenone. OGD decreased viability by 50 percent, depolarized mitochondria, and reduced mitochondrial respiration whereas DZ improved viability to 75 percent and suppressed reactive oxygen species production, but did not restore mitochondrial membrane potential after OGD. Diazoxide also increased phosphorylation of protein kinase B, mTOR, and S6K. Rapamycin, Torin-1, and S6K targeted siRNA abolished the protective effects of DZ. Co-application of L-NAME with DZ prevented preconditioning whereas adding SNP or DEANO along with L-NAME and DZ restored protection. Diazoxide increased phosphorylated nNOS. Interestingly, co-application of LNAME with DZ blocked the phosphorylation of nNOS as well as S6K. The ratio of phosphorylated/total Akt and mTOR were not significantly altered with L-NAME co-application. Diazoxide altered OCR 24 and 48 h after the ischemic period. Diazoxide had no acute effect on OCR but increased ECAR significantly. Activation of the mTOR and nNOS pathways is critical for DZ preconditioning in neurons. Furthermore, OCR is modified by the DZ-induced preconditioning of neurons. / acase@tulane.edu

Spontaneous intracerebral hemorrhage, the non-traumatic rupture of cerebral blood vessels, is the most devastating form of stroke. The disease is dynamic, unpredictable, and patients can worsen acutely within the first 24 hours secondary to hematoma expansion: re-bleeding of a baseline hemorrhage. Hematoma expansion is a major predictor of mortality and poor long-term outcome. This secondary analysis thesis proposes to advance the current understanding of this phenomenon through three separate research endeavors: 1) a scoping review of hematoma expansion prediction scores, 2) an independent validation of a non-contrast prediction score, and 3) an assessment and revision of the dichotomous definition of hematoma expansion used in clinical trials. These three projects will offer different contributions that will advance the science of intracerebral hemorrhage, a field where treatment options, outcome measures, and basic definitions, are all under active debate.

Mitochondria are dynamic organelles that constantly undergo opposing fission and fusion events which impact many aspects of mitochondrial and cellular homeostasis including bioenergetic activity, calcium buffering and organelle transport. The large GTPase dynamin-related protein 1 (Drp1) acts as a mechanoenzyme to catalyze fission of mitochondria. Drp1 activity is regulated through a series of reversible posttranslational modifications. Phosphorylation of the conserved serine residue, S656, by cAMP dependent protein kinase A (PKA) acts as a master regulator of Drp1 activity. Two phosphatases oppose PKA by dephosporylating Drp1 S656, a mitochondrial isoform of protein phosphatase 2A and the calcium-calmodulin dependent phosphatase calcineurin (CaN). Here I report the characterization of a conserved CaN docking site on Drp1, an LxVP motif, just upstream of the Drp1 S656 site. Mutational modification of the Drp1 LxVP motif resulted in selective bidirectional modulation of formation of the CaN:Drp1 complex. Stability of the CaN:Drp1 LxVP motif mutant complexes was qualitatively described by affinity purification and quantitatively described by isothermal titration calorimetry. Stability of the CaN:Drp1 complex was found to directly correlate with Drp1 S656 dephosphorylation kinetics as demonstrated by studies conducted in vitro and in intact cells. Further, the CaN:Drp1 signaling axis was shown to shape basal mitochondrial morphology in a heterologous cell line system and in primary hippocampal neurons. Finally, disruption of the CaN:Drp1 signaling axis was found to protect neurons from oxygen-glucose deprivation, an in vitro model of ischemic injury. While these results suggest that the CaN:Drp1 signaling axis may be a potential target for neuroprotective therapeutic exploitation, the mechanism by which disruption of the CaN:Drp1 signaling axis specifically and mitochondrial elongation generally results in resistance to ischemic injury remains unknown. Additional studies reported here demonstrate that mitochondrial fragmentation remains a prominent feature of injured neurons regardless of the fidelity of the CaN:Drp1 signaling axis. Mitochondrial fragmentation at the time of injury was found to occur in a Drp1-independent manner. Chronic mitochondrial elongation was also found to leave unaltered the ability of neurons to detoxify reactive oxygen species, buffer intracellular calcium and supply ATP for homeostatic function.

Human umbilical cord blood (HUCB) cells consist of a heterogeneous population of cells, rich in hematopoietic stem and progenitor cells. These cells have been used in the treatment of various nonmalignant and malignant hematopoietic diseases. With in the last few years HUCB cells have been used in pre-clinical animal models of brain and spinal cord injuries, in which functional recovery has been shown. The properties of cord blood cells that could be important in cell transplantation (repair or replacement) of CNS injury or disease are currently being evaluated. The major focus of this study was to determine whether HUCB cells would migrate to ischemic tissue extracts. In addition, factors that may be inducing the cells to migrate were examined by identifying the cytokines or chemokines present in the ischemic tissue extracts. The secondary focus was to establish whether cultured HCUB cells are releasing cytokines and chemokines (in vitro) in response to their environment. The results of these studies showed that HUCB cells migrate to ischemic tissue in a time dependent manner. In which there is a 48 to 72 hour window of opportunity for the delivery of HUCB cells to the ischemic brain. In addition, the cord blood cells were shown to release cytokines that may be aiding in the behavioral recovery seen in the transplantation studies. The results from this study are promising in that the current 3-hour therapeutic window for the treatment of stroke victims, using approved anticoagulant treatment, may be extended with the use of cord blood cell therapy with the peak at 48 hours.

The aim of this work was to develop devices for elite athletes to record performance related parameters during their training. A device was initially designed and built for rowing to record the motion of the boat. This was to gain understanding of motion signals in a one dimensional plane. The device uses a iPAQ handheld computer for recording and display of data to the user. Using the knowledge obtained from the accelerometer data of the rowing system an initial prototype device was designed and constructed for use in swimming. This device was required to be wearable whilst the swimmer was training, thus it had to record the data onboard. A second version of the swimming device was constructed to improve the usability of the device. The swimming device has fully sealed electronics, wireless charging and infrared communications. The device records three dimensional acceleration patterns at 150Hz, and can store over 6 hours of data using the internal memory. The device can operate for greater than 12 hours before needing to be recharged. The data collected from the swimming device was used to develop processing algorithms to extract when the swimmers push off from the wall, the type of stroke they are swimming, and for freestyle the stroke count. The results of the wall push off algorithm were compared against manual hand timing with 90% algorithm results being with ±1 second of the hand timing data. The stroke type identification algorithm determines which stroke is being swum and presently has an accuracy of 95%. The results of the freestyle stroke count algorithm were compared against manual stroke counts from raw accelerometers data and underwater video. Of the 164 data sets analysed over 90% of the algorithm results were within ±1 strokes of the manual recorded stroke counts.

There is increasing evidence that stroke survivors benefit from the provision of intensive, task-specific therapy in the rehabilitation of motor function. Providing such therapy to a number of stroke survivors in a group setting (know as circuit class therapy) has been proposed as an alternative model of physiotherapy service delivery within the inpatient rehabilitation setting. This study investigated the effectiveness and feasibility of circuit class therapy, as compared to the standard practice of one-to-one therapy sessions, within a representative sample of stroke survivors receiving inpatient rehabilitation.

<p>Bakgrund: Yngre personer som insjuknar i stroke har många unika problem som skiljer sig från de äldres. Den kroniska sjukdomen innebär begränsningar i det dagliga livet och påverkar deltagandet i olika aktiviteter. Sjukdomen påverkar inte bara den som insjuknar i stroke utan hela familjen. De yngre som insjuknar i stroke upplever hög nivå av ångest angående frågor rörande barnens uppväxt, att återvända till arbete och för många personer förlust av oberoende.</p><p>Syfte: Syftet var att genom systematisk litteraturstudie belysa hur yngre personer, under 65 år upplevde insjuknandet och att leva med sjukdomen stroke.</p><p>Metod: Studien genomfördes som en litteraturstudie. Sökningar gjordes via databaserna PubMed och Cinahl där 16 artiklar valdes som motsvarade syftet. Artiklarna analyserades med kvalitativ innehållsanalys med manifest ansats som resulterade i tre kategorier och elva underkategorier.</p><p>Resultat: Resultatet av litteraturstudien visade att yngre personer som insjuknar i stroke ofta hade kvarvarande emotionella och kognitiva skador som påverkade personligheten och som ofta var osynlig för omgivningen. Detta ledde till svårigheter i sociala relationer, känsla av övergivenhet och svårigheter att återgå till arbetet. Familjerelationer och roller liksom arbetsroller och jaget förändrades vilket ledde till känslor av att sakna kontroll och osäkerhet inför framtiden.</p><p>Slutsats: När vi som sjuksköterskor skall vårda med livsvärlden som ansats, ska vi bejaka patientens levda och komplexa verklighet och på så sätt blir de som insjuknat i stroke och de anhörigas perspektiv naturligt.</p>

<p>Syftet med denna uppsats var att få ökad förståelse för hur anhöriga till personer med stroke upplever och hanterar sin nya livssituation. Uppsatsen studerar med hjälp av copingteori vilka copingstrategier de anhöriga använder sig av och om val av copingstrategier skiljer sig åt mellan män och kvinnor. Detta undersöktes genom fem kvalitativa djupinterjuver varigenom jag fick tillgång till de anhörigas upplevelser. Analysen är uppdelad i tre teman: 1) Parrelation/familj 2) Socialt nätverk 3) Samhällsstöd. Citat ur interjuverna förstärker vad teori och tidigare forskning belyser. Resultat visar att respondenterna använder sig växelvis av problem- och känslofokuserade copingstrategier samt att val av copingstrategi inte beror på kön utan mer utifrån personlighet</p>

<p><strong>Bakgrund: </strong>Stroke är en vanlig sjukdom som drabbar många människor. Efter utskrivningen övertar ofta närstående vårdandet, vilket kan påverka de närståendes livssituation och livskvalitet. <strong>Syfte: </strong>Syftet med denna litteraturstudie var att belysa närståendes situation när de vårdar personer som har drabbats av en stroke, samt deras behov av stöd.<strong> Metod: </strong>Litteraturstudien innehåller sammanlagt 21 studier inom det valda området och dessa har sedan analyserats.<strong> Resultat: </strong>Resultatet presenteras i två huvudkategorier; upplevelser och stöd, samt i fyra underkategorier; graden av upplevd belastning, rollen som närståendevårdare och deras upplevda livskvalitet, behov av stöd och stöd från sjuksköterskan. Huvudresultatet i litteraturstudien berörde hur närståendevårdare till personer som har drabbats av en stroke upplevde sin livskvalitet, samt det stöd närståendevårdare kände att de var i behov av och stöd som givits till dem. <strong>Diskussion/Slutsats: </strong>Att se helhetsbilden kring personen som har drabbats av en stroke, vilket inkluderar deras närstående, är viktigt för att se vilket behov som finns efter utskrivningen från sjukhuset.<strong> </strong>Genom att lyssna på vad närståendevårdarna vill ha för typ av stöd och utveckla detta vidare finns det möjlighet att hjälpa livssituationen för framtidens närståendevårdare.</p>

<p>Stroke är en av våra stora folksjukdomar och årligen insjuknar 35 000 människor varav 20 procent är mellan 19 och 64 år. Det innebär stora omställningar i livet för de yngre i</p><p>arbetsför ålder som insjuknat i stroke då de ofta har en familj att ta hand om och ett arbete att gå till. Syftet med studien var</p><p>att belysa faktorer som påverkar de yngre patienterna vid återanpassning till livet efter stroke. Studien genomfördes</p><p>som en litteraturstudie där 12 vetenskapliga artiklar granskades. I resultatet framkom det att de yngre patienterna främst upplevde att information, rehabilitering, stöd och dolda funktionshinder är de faktorer som mest påverkar återanpassningen till livet efter stroke. De upplever att informationen inte är tydlig och att rehabiliteringen inte är individ- och åldersanpassad. De dolda funktionshindrena får ofta konsekvenser för patienterna. Familjens och omgivningens bemötande kan vara ett stöd för att uppnå en</p><p>bra återanpassning till livet. För att bättre kunna ge individuell och åldersanpassad omvårdnad vid stroke är det</p><p>av stor betydelse att sjuksköterskan ser helheten av patienterna och är flexibel samt lyhörd till deras livssituation.</p>