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Platelets act as a fundamental component of the hemostatic process and their activation leads to the formation of a stable clot at the injured endothelium surface. Thrombin, as the important physiological agonist, activates platelets through protease-activated receptors (PARs). Protease-activated receptors are one of the major receptors in platelets and belong to the seven-transmembrane G-protein couple receptor family. Four protease-activated receptors are found, named as PAR1, PAR2, PAR3 and PAR4. Human platelets express PAR1 and PAR4 and murine platelets express PAR4 and PAR3 instead of PAR1. Thrombin activates PARs through a unique mechanism, involving the cleavage of N-terminus of PAR receptors and the newly exposed N-terminus acts as its own tethered ligand to bind and activate the receptor. In this study, we characterized a new PAR1 specific activating peptide (TFRRRLSRATR), generated from the c-terminus of human platelet P2Y1 receptor, and evaluated its biological function. This peptide activated platelets in a concentration-dependent manner, causing shape change, aggregation, secretion and calcium mobilization. Its activation is completely inhibited by using BMS200261, a PAR-1 specific antagonist. Its specificity to PAR1 receptor is further confirmed by using TFRRR-peptide-pretreated washed platelets and murine platelets. The shape change induced by 10 microM peptide was totally abolished by Y-27632, an inhibitor of p160ROCK which is the downstream signal of G12/13 pathways. The TFRRR-peptide, YFLLRNP, and the physiological agonist thrombin selectively activated G12/13 pathways at low concentrations and began to activate both Gq and G12/13 pathways with increased concentrations. Similar to SFLLRN, the TFRRR-peptide caused phosphorylation of Akt and Erk in a P2Y12 receptor-dependent manner, and p-38 MAP kinase activation in a P2Y12-independent manner. The effects of this peptide are elicited by the first six amino acids (TFRRRL) whereas the remaining peptide (LSRATR), TFERRN, or TFEERN had no effects on platelets. Beside thrombin, PARs also can be activated by other proteases. Previous studies in our lab show that plasmin, a major extracellular protease, activates both human and murine platelets through prototypical cleavage of PAR4 (Quinton et al., 2004). In this study, we continue our study and investigate the molecular basis for the differential activation of murine and human platelets by plasmin. Plasmin-induced full aggregation is achieved at lower concentrations (0.1 U/mL) in murine platelets as compared to human platelets (1 U/mL). In COS7 cells expressing the murine PAR4 (mPAR4) receptor, 1 U/mL plasmin caused a higher intracellular calcium mobilization than in cells expressing the human PAR4 (hPAR4) receptor. This difference was reversed when the tethered ligand sequences of mPAR4 and hPAR4 were interchanged through site-directed mutagenesis. This difference between human and murine PAR4 is not because of the cofactor effect of PAR3 in murine platelets by showing that in both transfected cell lines and platelet system, PAR3 inhibits plasmin-induced PAR4 stimulation. All of the data suggest that murine platelets are more sensitive to activation by plasmin than human platelets due to differences in the primary sequence of PAR4. In contrast to thrombin-dependent activation of platelets, wherein PAR3 acts as a co-receptor, mPAR3 inhibits plasmin-induced PAR4 activation. Abnormal platelet activation causes thrombus formation and induces pathological conditions including stroke and atherosclerosis. Antithrombotic therapy is a widely used therapeutic method for stroke. However, currently used agents based on the irreversible inhibition of the platelet cyclooxygenases 1 and 2 or inhibition of P2Y12 receptors can cause unexpected bleeding or resistant side effects. Antithrombotic therapy targeting thrombin signaling is one of the new treatments under investigation and PAR1 antagonists are now in clinical trials. In this study, we investigate the effect of one of thrombin receptors, protease-activated receptor 4 (PAR4) in mice transient middle cerebral artery occlusion/ reperfusion (tMCAO/R) model. Our data show that PAR4 -/- mice have more than 80% reduction in infarct volume and significant improved neurological and motor function after 1 h MCAO followed by 23 h reperfusion. Examination of cellular responses to tMCAO/R indicates that PAR4-/- mice have less cellular death. Platelet/endothelial and leukocyte/endothelial interactions have been shown to play a critical role in the inflammatory responses during cerebral ischemic/reperfusion injury. Comparing wild-type with PAR4-/- mice platelets/endothelial and leukocyte/endothelial interactions, deficiency of PAR4 causes a significant decrease in both platelet/endothelial and leukocyte/endothelial interactions. In addition, PAR4-/- mice attenuate blood-brain barrier (BBB) disruption during tMCAO/R. All the data suggest that deficiency of PAR4 will protect against brain ischemic injury though attenuation of cerebral inflammatory responses including inflammatory cells extravasation and BBB disruption. Protease-activated receptor 4 (PAR4) is the only thrombin receptor existing in both human and murine platelets. The data we get in this study also have a beneficial effect for human study and inhibition of PAR4 may provide a novel potential therapeutic strategy for ischemic injury. / Physiology

In the healthcare system when a patient is waiting for a donated heart, the choice of the transportation method is critical. Thus, the efficiency of this procedure relies on the traveling time, which could affect the ischemic time, which is the time that heart can be discharged outside the human body. For best patient outcome, the heart has to be transplanted within four hours from the donor to the recipient. By transporting the donated heart via Unmanned Aerial Vehicle (UAV, or drone), both the time and the cost required for the heart transportation will be minimized. This thesis intends to explore the specifications needed for the design and manufacture of a heart container and pick-up system for a drone, which will be able to transport a donated heart between hospitals.

La pratique d’activité physique fait partie intégrante des recommandations médicales pour prévenir et traiter les maladies coronariennes. Suivant un programme d’entraînement structuré, serait-il possible d’améliorer la réponse à l’exercice tout en offrant une protection cardiaque au patient? C’est ce que semblent démontrer certaines études sur le préconditionnement ischémique (PCI) induit par un test d’effort maximal. Les mêmes mécanismes physiologiques induits par le PCI sont également observés lorsqu’un brassard est utilisé pour créer des cycles d’ischémie/reperfusion sur un muscle squelettique. Cette méthode est connue sous l’appellation : préconditionnement ischémique à distance (PCID). À l’autre extrémité du spectre de l’activité physique, des sportifs ont utilisé le PCDI durant leur échauffement afin d’améliorer leurs performances. C’est dans l’objectif d’étudier ces prémisses que se sont construits les projets de recherches suivants. La première étude porte sur les effets du PCID sur des efforts supra maximaux de courte durée. Les sujets (N=16) ont exécuté un test alactique (6 * 6 sec. supra maximales) suivi d’un test lactique (30 secondes supra maximales) sur ergocycle. Les sujets avaient été aléatoirement assignés à une intervention PCID ou à une intervention contrôle (CON) avant d’entreprendre les efforts. La procédure PCID consiste à effectuer quatre cycles d’ischémie de cinq minutes à l’aide d’un brassard insufflé à 50 mm Hg de plus que la pression artérielle systolique sur le bras. Les résultats de ce projet démontrent que l’intervention PCID n’a pas d’effets significatifs sur l’amélioration de performance provenant classiquement du « système anaérobie », malgré une légère hausse de la puissance maximal en faveur du PCID sur le test de Wingate de trente secondes (795 W vs 777 W) et sur le test de force-vitesse de six secondes (856 W vs 847 W). Le deuxième essai clinique avait pour objectif d’étudier les effets du PCID, selon la méthode élaborée dans le premier projet, lors d’un effort modéré de huit minutes (75 % du seuil ventilatoire) et un effort intense de huit minutes (115 % du seuil ventilatoire) sur les cinétiques de consommation d’oxygène. Nos résultats démontrent une accélération significative des cinétiques de consommation d’oxygène lors de l’intervention PCID par rapport au CON aux deux intensités d’effort (valeur de τ1 à effort modéré : 27,2 ± 4,6 secondes par rapport à 33,7 ± 6,2, p < 0,01 et intense : 29,9 ± 4,9 secondes par rapport à 33,5 ± 4,1, p < 0,001) chez les sportifs amateurs (N=15). Cela se traduit par une réduction du déficit d’oxygène en début d’effort et une atteinte plus rapide de l’état stable. Le troisième projet consistait à effectuer une revue systématique et une méta-analyse sur la thématique du préconditionnement ischémique (PCI) induit par un test d’effort chez les patients coronariens utilisant les variables provenant de l’électrocardiogramme et des paramètres d’un test d’effort. Notre recherche bibliographique a identifié 309 articles, dont 34 qui ont été inclus dans la méta-analyse, qui représente un lot de 1 053 patients. Nos analyses statistiques démontrent que dans un effort subséquent, les patients augmentent leur temps avant d’atteindre 1 mm de sous-décalage du segment ST de 91 secondes (p < 0,001); le sous-décalage maximal diminue de 0,38 mm (p < 0,01); le double produit à 1 mm de sous-décalage du segment ST augmente de 1,80 x 103 mm Hg (p < 0,001) et le temps total d’effort augmente de 50 secondes (p < 0,001). Nos projets de recherches ont favorisé l’avancement des connaissances en sciences de l’activité physique quant à l’utilisation d’un brassard comme stimulus au PCID avant un effort physique. Nous avons évalué l’effet du PCID sur différentes voies métaboliques à l’effort pour conclure que la méthode pourrait accélérer les cinétiques de consommation d’oxygène et ainsi réduire la plage du déficit d’oxygène. Nos découvertes apportent donc un éclaircissement quant à l’amélioration des performances de type contre-la-montre étudié par d’autres auteurs. De plus, nous avons établi des paramètres cliniques permettant d’évaluer le PCI induit par un test d’effort chez les patients coronariens. / Physical activity is an integral part of medical recommendations for preventing and treating coronary heart disease. By following a structured training program, is it possible to improve response to exercise and provide heart protection at the same time? This is suggested by certain studies on ischemic preconditioning (IPC) induced by a maximal exercise test. The same physiological mechanisms induced by IPC are also observed when a pressure cuff is used to create cycles of ischemia/reperfusion on skeletal muscle. This is known as remote ischemic preconditioning (RIPC). At the other end of the physical activity spectrum, athletes have used RIPC during warm-ups to improve performance. The following research projects were developed to study these premises. The first trial addressed the effects of RIPC on short supra-maximal exercise. The subjects (N = 16) performed an alactic test (six seconds of supra-maximal exercise) followed by a lactic test (30 seconds of supra-maximal exercise) on a cycle ergometer. The subjects were randomly assigned to an RIPC or CON intervention before the exercise. The RIPC procedure involved four cycles of ischemia using a pressure cuff inflated to 50 mmHg above systolic blood pressure at the arm. The results of the project show that RIPC intervention does not significantly improve performance typical of the anaerobic system, despite a slight increase in maximal power output in favour of RIPC in the 30 second Wingate test (795 W vs. 777 W) and in the 6 seconds test (856 W vs. 847 W). The aim of the second clinical trial was to study the effects of RIPC during eight minutes of moderate exercise (75% of ventilatory threshold) and intense exercise (115% of ventilatory threshold) on the kinetics of O2 uptake. Our results showed a significant acceleration in the kinetics of O2 uptake during the RIPC intervention compared to the CON intervention for the two exercise intensities (value of 1 during moderate exercise: 27.2 ± 4.6 seconds compared with 33.7 ± 6.2, p < .01 and intense exercise: 299 ± 4.9 seconds compared with 33.5 ± 4.1, p < .001) in amateur athletes (N= 15). This means a reduction in the oxygen deficit at the onset of exercise and more rapid achievement of the steady state. The third project involved performing a systematic review and meta-analysis on ischemic preconditioning (IPC) induced by an exercise test in coronary patients. Our literature search identified 309 articles, 34 of which were included in the meta-analysis, which represents a batch of 1,053 patients. Our statistical analyses show that in subsequent exercise, patients' time to 1 mm ST segment depression is augmented by 91 seconds (p < .001); the maximum depression decreases by 0.38 mm (p < .01); the double product at 1 mm ST segment depression increases by 1.80 x 103 mmHg (p < .001) and the total time of exercise increases by 50 seconds (p < .001). Our research projects have promoted the advancement of knowledge in exercise science by the use of a cuff as a stimulus to the RIPC before sports performance. We evaluated the effect of the RIPC on different metabolic pathways and we concluded that the method could accelerate the kinetics of oxygen consumption and reduce the range of oxygen deficit. In addition, we have established clinical parameters for assessing the IPC induced by a stress test for coronary patients. / Il praticare attività fisica è parte integrante delle raccomandazioni mediche atte a prevenire e trattare le coronopatie. Seguendo un programma di allenamento strutturato, sarebbe possibile migliorare la risposta all’esercizio, pur offrendo una protezione cardiaca al paziente: è ciò che sembrano dimostrare alcuni studi sul precondizionamento ischemico (PCI) indotto mediante test da sforzo massimale. Gli stessi meccanismi fisiologici indotti dal PCI vengono inoltre osservanti utilizzando una fascia da braccio per creare dei cicli d’ischemia/riperfusione su un muscolo scheletrico. Tale metodo è conosciuto con il nome di “precondizionamento ischemico a distanza” (PCID). All’estremità opposta dello spettro dell’attività fisica, alcuni sportivi hanno impiegato il PCID durante il riscaldamento, al fine di migliorare le proprie prestazioni. I seguenti progetti di ricerca sono stati elaborati con l’obiettivo di studiare queste premesse. Il primo studio riguarda gli effetti del PCID sugli sforzi sovramassimali di breve durata. I soggetti (N = 16) hanno effettuato un test anaerobico alattacido (6 x 6 sec. sovramassimali), seguito da un test anaerobico lattacido (30 secondi sovramassimali) su ergociclo. I soggetti sono stati aleatoriamente assegnati a un intervento di PCID o a un intervento di controllo (CON) prima di effettuare gli sforzi. La procedura di PCID consiste nell’effettuare quattro cicli d’ischemie con l’ausilio di una fascia da braccio a 50 mm Hg in più rispetto alla pressione arteriosa sistolica. I risultati del progetto dimostrano che l’intervento di PCID non ha effetti significativi sul miglioramento della prestazione proveniente classicamente dal “sistema anaerobico”, nonostante un leggero aumento di potenza a favore del PCID sul test di Wingate (795 W vs 777 W) di sei secondi (856 W vs 847 W). La seconda sperimentazione clinica aveva come obiettivo lo studio degli effetti del PCID durante uno sforzo moderato di otto minuti (75% della soglia ventilatoria) e intenso (115% della soglia ventilatoria) sulle cinetiche di consumo d’ossigeno. I nostri risultati dimostrano un’accelerazione significativa delle cinetiche di consumo d’ossigeno durante l’intervento di PCID rispetto al CON alle due intensità di sforzo (valore da 1 a sforzo moderato: 27,2 ± 4,6 secondi rispetto a 33,7 ± 6,2, p < 0,01 e intenso: 29,9 ± 4,9 secondi rispetto a 33,5 ± 4,1, p < 0,001) negli sportivi dilettanti (N= 15). Ciò si traduce con una riduzione del deficit di ossigeno all’inizio dello sforzo e un raggiungimento più rapido dello stato stazionario. Il terzo progetto consisteva nell’effettuazione di una revisione sistematica e una meta-analisi sulla tematica del precondizionamento ischemico (PCI) indotto mediante test da sforzo nei pazienti coronopatici. La nostra ricerca bibliografica ha individuato 309 articoli, 34 dei quali sono stati inclusi nella meta-analisi, che rappresentano un gruppo di 1.053 pazienti. Le analisi statistiche da noi effettuate dimostrano che in uno sforzo susseguente, i pazienti aumenti i loro tempi prima di raggiungere 1 mm di sottoslivellamento del segmento ST di 91 secondi (p < 0,001); il sottoslivellamento massimo diminuisce di 0,38 mm (p < 0,01); il doppio prodotto a 1 mm di sottoslivellamento del segmento ST aumenta di 1,80 x 103 mm Hg (p < 0,001) e il tempo totale di sforzo aumenta di 50 secondi (p < 0,001).

As técnicas de processamento digital de imagens têm sido vastamente aplicadas às imagens médicas. Um dos benefícios ocasionado por estas ferramentas é o de prover medidas de parâmetros que são difíceis de estimar e suscetíveis a viés do médico. O presente trabalho teve por objetivo desenvolver um software semi-automático de segmentação das áreas isquêmicas, core e penumbra, no acidente vascular cerebral, utilizando técnicas de segmentação por limiarização e baseada em regiões. Os dois algoritmos de segmentação (estatística local e limiarização) foram aplicados aos mapas de perfusão, calculados em um software separado, o stroketool-ct (Wittsack, University of Duesseldorf, Alemanha). Este software dispõe de três métodos de cálculo dos mapas, a partir das imagens de tomografia computadorizada de perfusão, que diferem no modelo matemático utilizado. O software aqui desenvolvido funciona como um módulo do stroketool-ct, não tendo acesso ao código fonte, apenas às estruturas de dados. O algoritmo de estatística local funciona através da expansão de uma amostra selecionada pelo usuário, na região isquêmica de interesse. Os resultados obtidos pelo algoritmo de estatística local foram comparados, através de um algoritmo de quantificação, com o padrão ouro, que consistiu na segmentação manual das regiões isquêmicas realizada pelo médico especialista. Respeitando as limitações pertinentes à técnica aplicada, os resultados obtidos pelo software de segmentação se mostraram satisfatórios. O algoritmo de limiarização utiliza os limiares fisiológicos de perfusão sangüínea estabelecidos na literatura para distinguir as áreas isquêmicas. A confiabilidade da segmentação reside no método específico de cálculo dos mapas de perfusão adotado. Além disso, os algoritmos fizeram o display dos resultados da segmentação em menos de 5 minutos em um computador pessoal, um tempo de espera razoável para o especialista que pode utilizar o resultado da segmentação do algoritmo para a tomada de decisão sobre a aplicação de terapia trombolítica / The techniques of digital image processing have been widely applied to medical imaging. One of the benefits brought about by these tools is to provide measurements of parameters that are difficult to estimate and likely to bias the physician. This study aimed to develop semi-automatic software of segmentation of the ischemic areas, core and penumbra in stroke, using techniques of thresholding and segmentation based on regions. The two segmentation algorithms (thresholding and local statistics) were applied to the perfusion maps that are calculated in a separate software, the stroketool-ct (Wittsack, University of Duesseldorf, Germany). This package provides three methods of calculation of maps, from images of perfusion computer tomography, which differ in the mathematical model used. The software developed here serves as a module stroketool-ct, not having access to source code, only the data structures. The statistical algorithm expands from a sample selected by the user, in the ischemic region of interest. The results obtained by the local statistical algorithm were compared by an algorithm of quantification with the gold standard, which is the manual segmentation of ischemic regions performed by the specialist. In spite of the limitations inherent to the technique applied, the results obtained by the local statistic algorithm were satisfactory. The thresholding algorithm uses the physiological perfusion thresholds established in the literature to distinguish the ischemic areas. The reliability of the segmentation obtained by thresholding algorithm resides on the specific method for the calculation of the perfusion maps that were adopted. Moreover, the algorithms provided the display of the segmentation results in less than 5 minutes in a standard computer, a reasonable waiting time for the specialist who can use the feedback to make the decision of whether applying the thrombolytic therapy

As técnicas de processamento digital de imagens têm sido vastamente aplicadas às imagens médicas. Um dos benefícios ocasionado por estas ferramentas é o de prover medidas de parâmetros que são difíceis de estimar e suscetíveis a viés do médico. O presente trabalho teve por objetivo desenvolver um software semi-automático de segmentação das áreas isquêmicas, core e penumbra, no acidente vascular cerebral, utilizando técnicas de segmentação por limiarização e baseada em regiões. Os dois algoritmos de segmentação (estatística local e limiarização) foram aplicados aos mapas de perfusão, calculados em um software separado, o stroketool-ct (Wittsack, University of Duesseldorf, Alemanha). Este software dispõe de três métodos de cálculo dos mapas, a partir das imagens de tomografia computadorizada de perfusão, que diferem no modelo matemático utilizado. O software aqui desenvolvido funciona como um módulo do stroketool-ct, não tendo acesso ao código fonte, apenas às estruturas de dados. O algoritmo de estatística local funciona através da expansão de uma amostra selecionada pelo usuário, na região isquêmica de interesse. Os resultados obtidos pelo algoritmo de estatística local foram comparados, através de um algoritmo de quantificação, com o padrão ouro, que consistiu na segmentação manual das regiões isquêmicas realizada pelo médico especialista. Respeitando as limitações pertinentes à técnica aplicada, os resultados obtidos pelo software de segmentação se mostraram satisfatórios. O algoritmo de limiarização utiliza os limiares fisiológicos de perfusão sangüínea estabelecidos na literatura para distinguir as áreas isquêmicas. A confiabilidade da segmentação reside no método específico de cálculo dos mapas de perfusão adotado. Além disso, os algoritmos fizeram o display dos resultados da segmentação em menos de 5 minutos em um computador pessoal, um tempo de espera razoável para o especialista que pode utilizar o resultado da segmentação do algoritmo para a tomada de decisão sobre a aplicação de terapia trombolítica / The techniques of digital image processing have been widely applied to medical imaging. One of the benefits brought about by these tools is to provide measurements of parameters that are difficult to estimate and likely to bias the physician. This study aimed to develop semi-automatic software of segmentation of the ischemic areas, core and penumbra in stroke, using techniques of thresholding and segmentation based on regions. The two segmentation algorithms (thresholding and local statistics) were applied to the perfusion maps that are calculated in a separate software, the stroketool-ct (Wittsack, University of Duesseldorf, Germany). This package provides three methods of calculation of maps, from images of perfusion computer tomography, which differ in the mathematical model used. The software developed here serves as a module stroketool-ct, not having access to source code, only the data structures. The statistical algorithm expands from a sample selected by the user, in the ischemic region of interest. The results obtained by the local statistical algorithm were compared by an algorithm of quantification with the gold standard, which is the manual segmentation of ischemic regions performed by the specialist. In spite of the limitations inherent to the technique applied, the results obtained by the local statistic algorithm were satisfactory. The thresholding algorithm uses the physiological perfusion thresholds established in the literature to distinguish the ischemic areas. The reliability of the segmentation obtained by thresholding algorithm resides on the specific method for the calculation of the perfusion maps that were adopted. Moreover, the algorithms provided the display of the segmentation results in less than 5 minutes in a standard computer, a reasonable waiting time for the specialist who can use the feedback to make the decision of whether applying the thrombolytic therapy

Successful cardiopulmonary resuscitation is the first step to rescue life during cardiac arrest. High mortality even after successful restoration of spontaneous circulation is substantially caused by patophysiological process associated with ischemia-reperfusion injury and it is widely called post-cardiac arrest syndrome (PCAS). There are many patophysiological mechanisms involved in the development and progress of this syndrom; the key role seems to play oxidative stress, triggering the activation cascade of systemic inflammatory reaction. In our study we have tested different possibilities of influencing the post-cardiac arrest syndrom. In the first experimental study we have compared the effect of mild therapeutic hypothermia with controlled normothermia on PCAS in a porcine model of cardiac arrest. In the second study we have compared in the same model the protective effects of mild therapeutic hypothermia, administration of nitric oxide and ischemic postconditioning. Results of the first experiment have revealed that mild therapeutic hypotermia is superior in the resuscitability, maintenance of blood pressure, oxidative stress suppression and organ damage protection than controlled normothermia. In the second experiment we have shown that neither nitric oxide administration, nor ischemic...

Tyrimo tikslas. Palyginti eisenos atsigavimą asmenims, patyrusiems trauminį galvos smegenų sužalojimą (TGSS) ar galvos smegenų infarktą (GSI), pirmajame reabilitacijos etape taikant kineziterapiją. Tyrimo uždaviniai.1) Įvertinti asmenų, patyrusių TGSS ar GSI, protinę būklę ir mobilumą prieš ir po kineziterapijos; 2) Įvertinti asmenų, patyrusių TGSS, eiseną taikant kineziterapiją pirmojo reabilitacijos etapo pradžioje ir pabaigoje; 3) Įvertinti asmenų, patyrusių GSI, eiseną taikant kineziterapiją pirmojo reabilitacijos etapo pradžioje ir pabaigoje; 4) Įvertinti asmenų, patyrusių TGSS ar GSI, proto būklės ir mobilumo atsigavimo įtaką eisenos atsigavimui, taikant kineziterapiją. Tyrimo metodai. Tyrime dalyvavo 60 asmenų: 30 asmenų, patyrusių TGSS, ir 30 asmenų, patyrusių GSI. Visiems tiriamiesiems buvo sutrikusi eisena. Vertinome tiriamųjų proto būklę pagal Trumpą Proto Būklės Tyrimo Testą, (TPBVT), mobilumą pagal Rivermead’o mobilumo indeksą (Rivermead Mobility Index) ir eiseną pagal Dinaminį Eisenos Indeksą (Dynamic Gait Index). Rezultatai skaičiuoti atliekant matematinę statistinę analizę. Visiems tiriamiesiems buvo taikoma kineziterapija siekiant eisenos atsigavimo. Tyrimo rezultatai. Tyrimo rezultatai parodė, kad taikant kineziterapiją pagerėjo proto būklė, mobilumas ir eisena abiejose tiriamųjų grupėse. Atlikus asmenų po TGSS ar GSI proto būklės, mobilumo ir eisenos palyginamąją analizę, gavome, kad kineziterapija turi teigiamą įtaką abiejų grupių proto būklės, mobilumo... [toliau žr. visą tekstą] / The aim. To compare gait recovery of individuals after Traumatic Brain Injury (TBI) or Ischemic Brain Stroke (IBS) using Physical Therapy during first rehabilitation stage. The tasks were: 1) To evaluate individuals after TBI or IBS mental state and mobility before and after Physical Therapy. 2) To evaluate individuals gait after TBI before and after Physical Therapy during first rehabilitation state. 3) To evaluate individuals gait after IBS before and after Physical Therapy during first rehabilitation state. 4) To find correlation between mental state, mobility and gait recovery of individuals after TBI or IBS using Physical Therapy. Methods and Material. In this study there were 60 persons participated: 30 after TBI and 30 after IBS. All patients had gait disorders. We evaluated mental state using Mini Mental State Examine (MMSE), mobility using Rivermead Mobility Index (RMI) and gait using Dynamic Gait Index. The results were calculated using mathematical statistical analysis. All patients received Physical Therapy to improve their gait. Results. The results showed significant mental state, mobility and gait recovery after Physical Therapy in both groups. Comparative analysis of persons after TBI or IBS mental state, mobility and gait showed that Physical Therapy has a statistically significant influence on mental state, mobility and gait recovery in both groups. We found correlation between mental state, mobility and gait recovery for patients after TBI or IBS. Gait... [to full text]

INTRODUCTION: The association of Sleep-Related Movement Disorders (SRMDs) such as Restless Legs Syndrome (RLS) and Periodic Limb Movements (PLMs) with cerebrovascular disease is underexplored. Emerging evidence links them to vascular disease, for which white matter hyperintensities (WMHs) are a well-recognized biomarker. METHODS: We conducted a cross-sectional hospital-based observational study in which high-risk TIA and minor stroke patients were assessed for vascular risk factors, WMHs and polysomnography-determined sleep variables. RESULTS: Ninety-seven patients were enrolled, of whom 44 completed polysomnography. Twenty-five percent had RLS, which was associated with lower quality of life. Independent of the effect of classical vascular risk factors, PLMs (but not RLS) were associated with WMHs on linear regression analyses (p=0.016). CONCLUSIONS: SRMDs are prevalent after minor stroke/TIA. RLS is associated with poor quality of life, while PLMs are associated with WMHs. Whether PLMs are implicated in the pathogenesis of WMHs or whether WMHs exacerbate PLMs remains uncertain.

<p>Cerebrovascular disease (stroke), especially ischemic stroke, is a major cause of death and neurological disability in adults. Because of its clinical heterogeneity, stroke is considered as a multi-factorial and polygenic disorder. Most current genetic studies of ischemic stroke focus on genetic susceptibility rather than factors determining stroke outcome. The genetic components of ischemic stroke outcome are difficult to study in humans due to environmental factors and medical intervention. Thus, we proposed to use a surgically induced, permanent, focal cerebral ischemic stroke mouse model to investigate genetic factors of ischemic stroke outcome measured by infarct volume. This model is the middle cerebral artery occlusion (MCAO) model. First, we screened infarct volumes across 32 inbred mouse strains. The infarct volume varies between strains, and this strongly suggests that infarct volume is genetically determined. To identify these genetic factors, we used genome-wide association study [Efficient Mixed-Model Association (EMMA) analysis] on infarct volume from 32 inbred mouse strains. Using the EMMA analysis, we identified 11 infarct volume-associated loci; however, most loci were mapped with missing alleles. This suggests that these loci might be false positives. Thus, we used specifically designed scripts of EMMA analysis with updated mouse SNP database to correct for potential false positives. The loci identified by the updated EMMA analyses will led us to the identification of genes involved in ischemic stroke outcome. </p><p> There are two major mechanisms were proposed to be determinants of infarct volume, the extent of native collateral circulation and neuroprotection. Using the infarct volume screening panel from 32 inbred strains, we observed that infarct volume is inversely correlated with the native collateral vessel number. However, among these inbred strains, we also observed several strains differ significantly in infarct volumes but harbor similar collateral numbers. In order to identify genetic factors determining infarct volume in a collateral-independent manner (neuroprotection), we used quantitative trait locus (QTL) mapping on mouse strains that exhibit the most difference in infarct volumes but the least difference in collateral numbers (C57BL/6J and C3H/HeJ). From the F2 B6 x C3H cross, we mapped 4 loci determining infarct volume (cerebral infarct volume QTL 4 to 7, Civq4 to Civq7). The Civq4 locus is the strongest locus (LOD 9.8) that contributes 21% of phenotypic variance in infarct volume. We also used a parallel F2 B6 x C3H cross to perform a QTL mapping on collateral vessel traits to further verify these collateral-independent loci. Among these 4 loci, the Civq4 and Civq7 loci appear to be truly collateral-independent. Based on strain-specific sequence variants and mRNA expression differences, we proposed Msr1 and Mtmr7 are the potential candidate genes of the Civq4 locus. Identification of the collateral-independent genetic factors will help to understand the genetic architecture, disease pathophysiology and potential therapeutic targets for of ischemic stroke</p> / Dissertation