Academic literature on the topic 'Intraparenchymal motility'

Varicocele, a vascular event, is associated with infertility due to testicular damage that causes abnormal spermatogenesis in males. The goal of this study is to ascertain the diagnostic significance of scrotal color Doppler ultrasonography (CDUS) by measuring peak systolic value (PSV) and resistive index (RI) of the arteries supplying blood to the testis and their association with semen quality attributes. Sixty prospective patients (age: 20-50 years) undergoing microsurgical varicocelectomy at a teaching hospital were included in the study. Semen parameters and CDUS were recorded and testicular blood flow was determined as PSV and RI of subcapsular artery and intraparenchymal artery of the testes. Nonparametric statistics was applied to test the correlation/association of the semen quality with the PSV, RI, and other variables. Results revealed a significant negative correlation (r = -0.28; p < 0.05) between progressive motility of spermatozoa and resistive index of the intraparenchymal arterial blood flow. Furthermore, it was noticed that the progressive motility of spermatozoa was tended to be negatively correlated (r = -0.236) with resistive index of subcapsular arterial blood flow. In conclusion, this study has revealed that progressive motility of sperms has correlation with the intraparenchymal blood flow of testes. The progressive motility of sperms could be correlated with RI of testicular blood flow. The apparent lack of association between diameter of varicocele vein and semen quality signifies the need of investigating some other factors that may be involved in pathogenicity of varicocele. The diagnostic value of CDUS may be carefully interpreted and clinically correlated in assessment of severity of varicocele.

Varicocele, is associated with infertility due to testicular damage that causes abnormal spermatogenesis in males. The goal of this study is to ascertain the diagnostic signicance of scrotal color Doppler ultrasonography (CDUS) by measuring peak systolic value (PSV) and resistive index (RI) of the arteries supplying blood to the testis and their association with semen quality attributes. Sixty prospective patients (age: 20-50 years) undergoing subinguinal varicocelectomy at a teaching hospital were included in the study. Semen parameters and CDUS were recorded and testicular blood ow was determined as PSV and RI of subcapsular artery and intraparenchymal artery of the testes. Nonparametric statistics was applied to test the correlation/association of the semen quality with the PSV, RI, and other variables. Results revealed a signicant negative correlation (r = -0.28; p < 0.05) between progressive motility of spermatozoa and resistive index of the intraparenchymal arterial blood ow. Furthermore, it was noticed that the progressive motility of spermatozoa was tended to be negatively correlated (r = -0.236) with resistive index of subcapsular arterial blood ow. In conclusion, this study has revealed that progressive motility of sperms has correlation with the intraparenchymal blood ow of testes. The progressive motility of sperms could be correlated with RI of testicular blood ow. The apparent lack of association between diameter of varicocele vein and semen quality signies the need of investigating some other factors that may be involved in pathogenicity of varicocele. The diagnostic value of CDUS may be carefully interpreted and clinically correlated in assessment of severity of varicocele.

Background: Varicocele is one of the leading causes of infertility in men. Resistance index (RI) in testis is a parameter indicating parenchymal perfusion and microvascular functions. Increased RI in the testis of patients with varicocele might be a sign of impairments in microvascularization and a significant decrease in testicular perfusion. In the present study, RI in capsular and intraparenchymal testicular arteries was evaluated in patients with varicocele who underwent varicocelectomy. Methods: This prospective cohort study was performed in 2019-2020 in Guilan, Iran. Sixty-six patients were included. Semen analysis was also done before surgeries. Patients with at least one disorder in semen analysis entered the study. RI in testicular arteries was measured by an experienced radiologist before surgeries. Six months after varicocelectomy, all patients underwent the same semen analysis and ultrasound imaging. Data were analyzed using SPSS software. The tests for analysis included McNemar Test and Wilcoxon and p<0.005 was considered as the significance level. Results: According to the results, 42 patients (63.6%) had positive changes in sperm analysis after surgeries. Sperm analysis showed a significant increase in number, concentration, morphology, and motility of sperm after surgeries (p<0.001). Further measurements of capsular and intratesticular RI in all patients also indicated a significant decrease (p<0.001). Conclusion: Increased RI might be associated with impaired microperfusion in testis followed by impairments in semen. Moreover, mean capsular and intratesticular RI in patients decreased after surgeries and this decrease was significantly more in patients who had improvement in their semen parameters.

Scientific Program Oral Presentations Authors Title Abstract CONSTANTIN MUNTEANU, Mihail HOTETEU, Diana MUNTEANU, Gabriela DOGARU - 12 minutes PERSPECTIVES OF BALNEOLOGY - INTERNATIONAL DATA INPUTS, NATIONAL OUTPUTS Link L1 UMBERTO SOLIMENE - 14 minutes CLIMATE AND HEALTH: A NEW CHALLENGE FOR AN OLD SCIENCE Link L2 Zeki KARAGÜLLE - 14 minutes BALNEOLOGICAL TREATMENTS WITH NATURAL HYDROGEN SULFIDE (H2S) Waters Link L3 Constantin Florin Dragan, Liliana Padure, Gelu Onose - 12 minutes SPECIFIC ADVANCED QUANTIFICATIONS ON THE RELATIONSHIP BETWEEN THE ANGULATION OF THE MAIN SCOLIOTIC CURVE AND LEG SWING IN THE GAIT PHASES, IN CHILDREN AND ADOLESCENTS WITH AND WITHOUT POSTURAL TREATMENT Link L4 Irina ALBADI, Camelia CIOBOTARU, Andreea-Alexandra LUPU, Ionela BALASA, Claudiu FATU, Enghin SACHIR, Gelu ONOSE - 12 minutes A MULTIMODAL APPROACHES TO MANAGE REHABILITATION THERAPY OF DISFUNCTIONALS ASPECTS TO A PACIENT WITH GOUT, MIELLITUS DIABETES, ATRIAL FIBRILATION AND MIDDLE CEREBRAL ARTERY STROKE Link L5 ELENA RAEVSCHI - 12 minutes PREVENTION CONSIDERATIONS IN Cardiovascular Diseases regarding the premature mortality reduction Link L6 ANIȘOARA CIMIL - 12 minutes THE EFFECTIVENESS OF THE REHABILITATION PROGRAMME ACCORDING TO THE ETIOPATHOGENESIS OF PROSTHETIC JOINT PATHOLOGY Link L7 TRAIAN -VIRGILIU SURDU, Monica SURDU, Olga SURDU - 10 minutes FOURTH INDUSTRIAL REVOLUTION (INDUSTRY 4.0) AND MODERN THERMAL MEDICINE (THERME 4.0) IN XXIST CENTURY Link L8 Gabriela DOGARU, Akos MOLNAR, Marieta MOTRICALA - 10 minutes EFFECTS OF CARBONATED MINERAL WATER AND MOFETTE IN BĂILE TUŞNAD IN EXPERIMENTALLY INDUCED ISCHEMIC HEART DISEASE Link L9 Q & A – 12 minutes Authors Title Abstract Aurelian Anghelescu, Valentin Deaconu, Catalina Axente,Elena Constantin, Gelu Onose - 12 minutes THERAPEUTIC DIFFICULTIES IN A YOUNG PATIENT WITH MULTIDRUG RESISTANT EPILEPSY (NEEDING VAGAL NERVE ELECTROSTIMULATION), SEQUELAE AFTER CONGENITAL VASCULAR CEREBRAL MALFORMATION, WITH CHRONIC GAIT IMPAIRMENTS AND RECENT TRAUMATIC BRAIN COMPLICATION Link L10 Luminița NIRLU, Alexandru G. STAVRICĂ, Laura Georgiana Popescu, Ana Carmen Albeșteanu, Ali-Osman Saglam, Gelu Onose - 12 minutes DIAGNOSTIC PARTICULARITIES AND MULTIMODAL THERAPEUTIC AND REHABILITATION APPROACHES TO A COMPLEX CASE OF POST ISCHEMIC STROKE WITH DYSPHAGIA AND DYSPHONIA, ASSOCIATING MILLARD-GUBLER AND WALLENBERG SYNDROMES - CASE REPORT Link L11 Cristina Octaviana DAIA, Croitoru Stefana, Mariana Axente, Gelu ONOSE - 14 minutes IONTOPHORESIS AND LASER APPLICATIONS IN FACIAL NERVE PALSY Link L12 Doina Maria MOLDOVAN, Gabriela DOGARU - 12 minutes SPLINTING VERSUS SURGICAL TREATMENT IN MALLET FINGER Link L13 Doina Maria MOLDOVAN, Gabriela DOGARU - 12 minutes EARLY REHABILITATION IN PATIENT AFTER TREATMENT FOR DISTAL RADIUS FRACTURE Link L14 Liliana PADURE, Raluca PETCU, Anca Irina GRIGORIU - 12 minutes THE IMPACT OF MULTIFACTORIAL GAIT ANALYSIS ON THE DIAGNOSIS AND REHABILITATION OF CHILDREN WITH WALKING DISORDERS Link L15 Valerica Creanga-Zarnescu, Ana-Maria Fatu, Mihaela Lungu, Violeta Sapira, Anamaria Ciubara - 12 minutes REHABILITATION POSSIBILITIES OF APHASIC PATIENT Link L16 Cristina DAIA, Simona SCHEK, Stefana CROITORU, Alina GHERGHICEANU, Gelu ONOSE - 12 minutes FAVORABLE REHABILITATION RESULTS ON A PATIENT WITH SEVERE LEFT HEMIPLEGIA AFTER AN INTRAPARENCHYMAL HEMATOMA Link L17 Elena VIZITIU, Mihai CONSTANTINESCU, Sînziana Călina SILIȘTEANU - 12 minutes THE ROLE OF THERAPEUTIC SWIMMING IN THE PROPHYLAXIS OF SCOLIOSIS IN THE "C" LEFT IN CHILDREN DURING THE PREPUBERTAL PERIOD Link L18 Q & A – 12 minutes Authors Title Abstract Alexandru G. STAVRICĂ, Luminiţa Nirlu, Laura Georgiana Popescu, Ana Carmen Albeşteanu, Gelu ONOSE - 12 minutes DIAGNOSTIC AND THERAPEUTIC APPROACHES IN REHABILITATION CORRELATED TO A CASE OF TETRAPARESIS (WITH PREDOMINANCE OF PARAPARESIS) AFTER SEVERE CCT - BIFRONTO - BASAL AND BITEMPORAL CONTUSION. Link L19 Ana Maria Bumbea, Otilia Rogoveanu, Carmen,Albu Rodica Traistaru, Catalin,Bostina, Bogdan Stefan Bumbea, Roxana Dumitrascu, Borcan Madalina MANAGEMENT OF SPASTICITY IN NEUROLOGICAL PATIENTS Link L20 Laura Georgiana Popescu, Luminița Nirlu, Ana Carmen Albeșteanu, Ali Osman Saglam, Gelu Onose - 12 minutes PARTICULARITIES OF COMPLEX THERAPEUTICALLY-REHABILITATIVE MANAGEMENT, STEPWISE, IN A PATIENT WITH POST-CCT PSYCHO-COGNITIVE IMPAIRMENT IN A LARGE POLYTRAMATIC CONTEXT - CASE REPORT Link L21 Adrian MELNIC, Oleg PASCAL - 12 minutes DEVELOPING STRATEGIES TO ADDRESS COMORBIDITY IN STROKE REHABILITATION. Link L22 Dorin-Gheorghe TRIFF, Simona POP - 12 minutes MONOGENIC DISEASES WITH MUSCULO ARTICULAR LAXITY. DIAGNOSTIC CRITERIA AND PRINCIPLES OF RECOVERY THERAPY Link L23 Catalin Ionite, Dragos Arotaritei, Mihai Ilea, Mariana Rotariu - 12 minutes THE USE OF ELASTIC BANDS IN THE RECOVERY OF ANKLE SPRAINS Link L24 Mariana Rotariu, Marius Turnea, Calin Corciova, Catalin Ionite - 12 minutes THE EFFECTS OF CUBE THERAPY IN THE RECOVERY OF THE ARTHROSIS HAND IN GERIATRICS Link L25 Cristian Ştefan LIUŞNEA - 12 minutes FITNESS AND WELLNESS. CONCEPTUAL DELIMITATIONS Link L26 Adriana LUPU - 12 minutes NSAID THERAPY OF MUSCULOSKELETAL PAINS AND ITS PARTICULARITIES IN THE PATIENTS SUFFERING FROM CARDIOVASCULAR DISORDERS Link L27 Q & A – 12 minutes Authors Title Abstract Mihaela MANDU, Cristinel Dumitru BADIU, Raluca PETCU, Cosmin OPREA, Gelu ONOSE - 12 minutes CLINICAL-EVOLUTIVE PARTICULARITIES AND A MULTIMODAL THERAPEUTIC-REHABILITATIVE, AS WELL AS THROUGH CONNECTED CARES, APPROACH, IN A CASE OF HEMIPLEGIA AFTER ISCHEMIC CARDIO-EMBOLIC STROKE WITHIN A POLYPATHOLOGICAL CONTEXT Link L28 Ana Carmen Albesteanu, Laura Georgiana Popescu, Luminița Nirlu, Ali Osman Saglam, Gelu Onose - 12 minutes MULTIMODAL - REHABILITATIVE THERAPEUTICAL APPROACHES IN A COMPLEX OF PATHOLOGY INCLUDING POSSIBLY EVOLVING DISCARIOTIC TYPE - CASE REPORT Link L29 Liliana PADURE, Cristian Adam, Laura Fierbinteanu - 12 minutes ATTACHMENT - PROGNOSTIC FACTOR IN MEDICAL RECOVERY Link L30 Prof. Alexandru Vlad Ciurea - 20 minutes MOTILITY OR MORBIDITY IN NEUROSURGERY Link L31 Valerica CREANGA-ZARNESCU, Ana-Maria FATU, Anamaria CIUBARA, Violeta SAPIRA,Aurelia ROMILA, Mihaela LUNGU - 12 minutes EXERCISES PROGRAM AND REHABILITATION IN PARKINSON’S DISEASE Link L32 Irina VERINCEANU,Alice MUNTEANU, Andreea STOICA, Stefan ISPAS - 12 minutes THE CARDIAC REHABILITATION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION Link L33 Marius Turnea, Catalin Ionite, Mihai Ilea, Dragos Arotaritei - 12 minutes STATISTICAL ANALYSIS OF PHYSIOTHERAPEUTIC MEANS USED IN THE RECOVERY OF MUSCLE INJURIES IN ATHLETES Link L34 Mihaiela CHICU, Eugen BITERE - 10 minutes THE ROLE OF IL1β IN CARTILAGINOUS DISTRUCTION IN RHEUMATOID ARTHRITIS Link L35 Mihaiela CHICU, Eugen BITERE - 10 minutes THE ROLE OF THE INFLAMMASOMS IN THE PATHOGENESIS OF INFLAMMATORY REACTION Link L36 Q & A – 8 minutes Authors Title Abstract Prof. Dr. Gelu Onose, (Keynote Speaker) Vlad Ciobanu, Corina Sporea - 20 minutes A TOPICAL SYSTEMATIC LITERATURE REVIEW AND REAPPRAISAL ON ESSAYS TOWARDS SYSTEMATIZING CLINICAL ASSESSMENT INSTRUMENTS USED TO EVALUATE NEURO-functional deficits after spinal cord injuries, mainly in adults, including through the ICF(-DH) conceptual framework Link L37 Diana-Elena SERBAN, Aurelian ANGHELESCU, Elena CONSTANTIN, Gelu ONOSE - 12 minutes THE ACQUISITION OF SELF-DEFENSE TECHNIQUES AND PROCEDURES AGAINST THE ACT OF AGGRESSION IN THE PACIENT WITH PARAPLEGIA, WHEEL-CHAIR INDEPENDENT Link L38 Aurelian Anghelescu, Elena Constantin, Anca Sanda Mihaescu, Gelu Onose - 12 minutes “PREVENTION IS CURE, EDUCATION IS ESSENTIAL” - RESPONSIBLE IMPLICATION OF YOUNG PEOPLE IN EDUCATIONAL AND PROPHYLACTIC ACTIONS AGAINST ACCIDENTAL CERVICAL SPINAL CORD INJURY AND SEVERE DISABILITIES BY DIVING IN UNVERIFIED WATERS. Link L39 Alexandra SPORICI, Irina ANGHEL, Lapadat MAGDALENA, Gelu ONOSE - 12 minutes RECOVERABLE RESULTS AT A PATIENT WITH AIS/FRANKEL D INCOMPLETE TETRAPLEGIA / POST SPINAL CORD INJURY BY FALLING FROM A HEIGHT, ON AN ANKYLOSING SPONDYLITIS BACKGROUND Link L40 Ioana ANDONE, Carmen CHIPĂRUȘ, Andreea FRUNZA, Aura SPÎNU, Simona STOICA, Liliana ONOSE, George PATRASCU, Gelu ONOSE -12 minutes CLINICAL, PARACLINICAL ASPECTS AND COMPLEX THERAPEUTICAL APPROACHES IN A PATIENT WITH INCOMPLETE PARAPLEGIA, POST THORACIC MENIGIOMA SURGICALLY TREATED, IN NEUROFIBROMATOSIS CONTEXT Link L41 Cristina Octaviana DAIA, Alina-Elena Gherghiceanu, Helene Ivan, Gelu ONOSE - 12 minutes RESEARCH ON NEUROREHABILITATION RESULTS IN VERTEBRO-MEDULLARY POST-TRAUMATIC CONDITIONS ASSOCIATING FRACTURES, IN A POLITRAMATIC CONTEXT Link L42 Ali-Osman Saglam, Alexandru G. Stavrica, Ana Carmen Albeşteanu, Laura Georgiana Popescu, Luminita Nirlu, Gelu Onose - 12 minutes MEDICAL-REHABILITATION ENDEAVORS, CARE INTERVENTIONS AND CONNOTATIONS OF A MEDICO-SOCIAL TYPE, IN A COMPLEX POLYPATHOLOGICAL CASE: PARAPLEGIA, SPONDYLODISCITIS, KIDNEY FAILURE IN THE HAEMODIALYSIS STAGE AND BILATERAL NEPHROSTOMIES AFTER SURGICALY TREATTED BLADDER NEOPLASM. Link L43 Sorina Petrușan-Dunca, Liviu Lazăr, Tiberiu-Dorin Corha - 12 minutes INDICATIONS AND LIMITIS OF REHABILITATION TREATMENT FOR LUMBAR DISCOPATHY IN PREGNACY Link L44 Q & A – 8 minutes Authors Title Abstract Elena Silvia SHELBY, Mihaela AXENTE, Liliana PĂDURE - 12 minutes CHARCOT MARIE TOOTH DISEASE. CASE PRESENTATION. 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Souto Figueroa, Antonio Freire Magariños RESEARCH - SURVEY TO 142 THERMALIST WHO HAVE PERFORMED A THERMAL CURE AT THE BATHS OF BAÑOS DE MOLGAS (OURENSE) AND AUGAS SANTAS (LUGO) - GALICIA – SPAIN Link L53 Q & A – 12 minutes Authors Title Abstract Irina Ionica - 12 minutes ACUPUNCTURE IN REHABILITATION - A GENERAL VIEW Link L54 Denisa COAJĂ, Gabriela DOGARU - 12 minutes THE HEALTH BENEFITS OF FINNISH SAUNA BATHING Link L55 Otilia ROGOVEANU, Florin GHERGHINA , Rodica TRAISTARU - 12 minutes SPINA BIFIDA – FUNCTIONAL REHABILITATION METHODS IN CHILDREN Link L56 Mihaela DUTESCU, Raluca OLTEAN, Petru NENADICI - 12 minutes GEOAGIU BAI RESORT - OUR EXPERIENCE OF MEDICAL REHABILITATION TREATMENT Link L57 Dumitru MIHĂILĂ, SILISTEANU Sinziana Calina, ȚICULEANU Mihaela (Ciurlică) - 12 minutes THE METEOROLOGICAL COMPLEX AND THE HUMAN PATHOLOGY. 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La Sclerosi Multipla (SM) è una patologia infiammatoria autoimmune cronica, disabilitante e demielinizzante, del sistema nervoso centrale (SNC). La migrazione di cellule T autoreattive e la loro riattivazione attraverso la presentazione antigenica effettuata dalle locali cellule presentanti l’antigene, rappresentano due eventi critici nella patogenesi della SM e nel suo modello animale, l’encefalite autoimmune sperimentale (EAE). Le risposte ai potenziali antigeni all’interno del SNC richiedono una migrazione a lungo raggio, comunicazione a corto raggio e contatti cellula-cellula diretti con le cellule presentanti l’antigene. Il principale obiettivo di questo studio è indagare il ruolo delle integrine L2 (LFA-1) e 4 (VLA-4 and 47) nella migrazione e nella motilità delle cellule autoreattive Th1 e Th17 in corso di EAE all’interno del midollo spinale utilizzando le moderne tecniche di microscopia intravitale. La microscopia intravitale permette di visualizzare questi processi dentro il midollo spinale, il quale rappresenta il principale sito di infiammazione durante l’EAE. Mediante la microscopia intravitale in epifluorescenza abbiamo prima di tutto investigato il ruolo delle integrine 4 e LFA-1 nella migrazione delle cellule autoreattive Th1 e Th17 all’interno dei vasi piali del midollo spinale durante la fase preclinica, l’esordio e la fase cronica di EAE. Abbiamo utilizzato un modello di EAE immunizzando topi C57BL/6 con il peptide MOG35-55. Le cellule Th1 e Th17 MOG-specifiche sono state prodotte in vitro da topi TCR-transgenici 2D2, marcate con label fluorescenti e iniettate in endovena nei topi immunizzati direttamente prima dell’acquisizione. I nostri risultati pongono l’accento su un ruolo selettivo per l’integrina LFA-1 nella migrazione delle cellule Th1 in particolare durante le prime fasi di malattia. Ruolo che invece non è svolto in fase cronica di malattia. Inoltre, il blocco della subunità 4, ma non dell’integrina 47 inibisce fortemente sia il rotolamento sia l’adesione stabile delle cellule Th1 all’endotelio infiammato. Questo suggerisce l’integrina VLA-4 come principale mediatrice della migrazione delle Th1 nel SNC infiammato in corso di EAE. Di notevole interesse è inoltre il selettivo ruolo per l’integrina 47 evidenziato in particolare nell’adesione stabile esclusivamente delle cellule Th17 all’esordio ed in fase cronica di malattia. Successivamente, per studiare la motilità intraparenchimale delle cellule Th1 e Th17 nel midollo spinale durante la fase preclinica della patologia, il picco di malattia e la fase cronica abbiamo utilizzato la microsocopia laser a due fotoni. I nostri risultati dimostrano una massiva infiltrazione di Th1 e Th17 nel parenchima del SNC al picco di malattia, mentre la migrazione di queste cellule durante le altre fasi della malattia è significativamente minore. In seguito, il nostro studio si è focalizzato sulla fase clinica della malattia e abbiamo osservato che le cellule Th1 e le cellule Th17 mostrano differenze significative nelle componenti direzionali, con le cellule Th1 che si muovono velocemente in direzione rettilinea, coprendo lunghe distanze nel parenchima del midollo spinale, mente le cellule Th17 girano intorno in un volume specifico del tessuto facendo stop and go. In particolare, il blocco dell’integrina LFA-1 influenza drasticamente le dinamiche delle cellule, portando ad una riduzione nella velocità e interferendo con il loro pattern di motilità rettilinea. Inoltre, in presenza di un anticorpo bloccante anti-LFA-1, le cellule Th17 mostrano una riduzione di velocità drastica. Diversamente, l’anticorpo anti-4 non ha nessun effetto sul comportamento motile delle Th1, ma riduce fortemente la velocità delle Th17 suggerendo che l’integrina VLA-4 non sia richiesta per la motilità intraparenchimale durante l’EAE. Tuttavia, alla luce dei risultati ottenuti in precedenza mediante microscopia intravitale, va preso in considerazione un selettivo ruolo esercitato dall’integrina 47 nella motilità intraparenchimale delle Th17. Complessivamente, i nostri risultati suggeriscono che l’LFA-1 sia la principale integrina che controlla la motilità delle cellule Th1 e Th17 e che 47 sia invece selettivamente coinvolta nella motilità delle cellule Th17 nel midollo spinale in condizioni infiammatorie al picco di malattia. A sostegno di questi risultati abbiamo testato un trattamento terapeutico mediante blocco locale, a livello intratecale, delle integrine LFA-1 e 47 nel nostro modello murino di EAE cronica. Entrambi i trattamenti hanno evidenziato una riduzione nello sviluppo della malattia che suggerisce l’importanza di interferire direttamente con le dinamiche delle cellule pro infiammatorie a livello del SNC. Approfondire dunque la conoscenza dei meccanismi molecolari che controllano la motilità intratissutale di cellule T attivate nel SNC potrebbe aiutarci a identificare nuove strategie terapeutiche per le patologie autoimmuni cerebrali croniche.
Multiple sclerosis (MS) is a chronic disabling autoimmune inflammatory demyelinating disease of the central nervous system (CNS). The migration of autoreactive T cells from the blood into the CNS and their reactivation through antigen presentation by local antigen presenting cells (APCs) represent critical events in the pathogenesis of MS and its animal model, the experimental autoimmune encephalomyelitis (EAE). The responses to potential antigens inside the CNS require long-range migration of cells, short-range communication and direct cell-cell contact with APCs. The main goal of this study was to investigate the role of L2 (LFA-1) and 4 (VLA-4 and 47) integrins in the migration and motility behavior of Th1 and Th17 cells, which represent key players in the induction of EAE, using intravital microscopy approaches. Intravital microscopy techniques allow the visualization of T cell migration and reactivation in the spinal cord (SC), which represents the main inflammation site during EAE. By using epifluorescence intravital microscopy (IVM) we first studied the roles of 4 and LFA-1 integrins in Th1 and Th17 cell adhesion in the pial vessels of spinal cord (SC) venules in mice immunized with MOG35-55 peptide during the preclinical phase, disease onset and chronic phase of disease. We used an EAE model by immunization of C57BL/6 mice with MOG35-55 peptide. MOG35-55-specific Th1 and Th17 cells were produced in vitro from 2D2 TCR transgenic mice, labeled with fluorescent dyes and intravenously injected in immunized mice before imaging. Our results underlined a selective role for LFA-1 integrin in Th1 cell recruitment in inflamed SC vessels during the early phases of the disease but not during the chronic phase. Moreover, blocking antibodies against the 4subunit, but not blockade of 47 integrin greatly inhibited rolling and firm adhesion of Th1 cells in the SC venules during all disease phases, suggesting that VLA-4 is the major molecule involved in Th1 cell adhesion in the SC venules during EAE. Interestingly, blockade of 47 integrin led to a significant reduction of firm adhesion in Th17 cells at the onset and chronic phase of EAE indicating a selective role of 47 integrin in the recruitment of Th17 cells in the inflamed CNS. Taking advantage of two-photon laser microscopy (TPLM) approach we next investigated the motility behavior of fluorescently labeled Th1 and Th17 cells within SC parenchyma during different disease phases. Our results showed a massive infiltration of Th1 and Th17 cells in the CNS parenchyma at disease peak, whereas the migration of these cells during other phases of disease was significantly lower. Furthermore, Th1 and Th17 cells displayed significant differences in the directional component, with Th1 cells moving faster in straight directions covering long distances deep in the SC parenchyma, whereas Th17 cells moved around in a specific volume of tissue in a stop and go mode. Notably, the blockade of LFA-1 integrin drastically affected the dynamics of Th1 cells leading to a reduction in velocity and interfering with their straight-line motility pattern. Moreover, Th17 cells displayed a drastic reduction of velocity in the presence of a blocking anti-LFA-1 antibody. The analysis of cellular morphology suggested that LFA-1 is actively involved in the cytoskeleton rearrangements necessary for T cell amoeboid migration inside the CNS, but had no role in the cytoskeleton dynamics in Th17 cells. Notably, 4integrins had no role in Th1 cells motility, but drastically reduced the dynamics of Th17 cells inside the SC parenchyma. To check the therapeutic relevance of our intravital microscopy findings, we performed intrathecal injection of anti-LFA-1 or anti-47 antibodies at disease onset and observed a significant inhibition of EAE progression in mice immunized with MOG35-55 peptide. Collectively, our data demonstrate that LFA-1 integrin differently controls intraparenchymal Th1 and Th17 cells dynamics, whereas 47 integrin is selectively involved in Th17 cell trafficking in the CNS during EAE. Furthermore, our results suggest that interfering with the molecular mechanisms controlling intraparenchymal dynamics of activated T cells may represent a new therapeutic strategy for CNS autoimmune diseases.