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PO10-TU-11 Chemokine receptors on regulatory T cells in experimental model of multiple sclerosis
S198
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
PO10-TU-10 A novel free radical scavenger: platinum nanoparticle improves neurological signs and electrophisiological findings in a rat EAE model via quenching ROS and NO H. Yoshida. Dept. of Neurology, Inst. of Neurology, University College London, London, United Kingdom Platinum nanoparticles were prepared by an alcohol reduction method and complementarily stabilized with polyacrilic acid (PAAPt). The average diameter of PAA-Pt was about 2nm. They were well dispersed in water and became colloidal solution. PAA-Pt efficiently quenched superoxide anion (O2 − ), Hydrogen peroxide (H2 O2 ) and Nitric oxide (NO). This quenching activity against ROS and NO persisited like catalysis such as SOD or catalase. Therefore, PAA-Pt may be a useful scavenger which is effective on medical treatment of oxidative stress diseases. In fact, we have shown that platinum nanoparticles are effective on animal models of various ROSrelated diseases like stroke, Alzheimer’s disease, Huntinton disease and so on. And this time, we evaluated the effect of PAA-Pt on experimental autoimmune encephalomyelitis (EAE) using a rat. Intravenous injection of PAA-Pt improves neurological signs and electrophysiological findings in an EAE rat model. PO10-TU-11 Chemokine receptors on regulatory T cells in experimental model of multiple sclerosis A. Glabinski, I. Jatczak, M. Pietruczuk. Medical University of Lodz, Lodz, Poland Purpose: Experimental autoimmune encephalomyelitis (EAE) is a well known animal model of multiple sclerosis (MS), the most common human central nervous system (CNS) demyelinating disease of putative autoimmune pathogenesis. The major goal of this study was to analyze the chemokine receptors expression on regulatory T cells from the CNS, blood, lymph nodes and spleen during different stages of development of EAE. Method: EAE was induced by immunization of female (SJLxSWR)F1 mice with 139–151 PLP peptide. Expression of CCR3, CCR6, CXCR4 and CXCR5 on Tregs was analyzed by flow cytometry in unimmunized control animals, animals with EAE during preclinical phase of the disease, as well as during the acute attack and the disease remission. Results: The number of Tregs in the CNS was constantly increasing during the preclinical phase, acute attack and remission of EAE. In the blood, lymph nodes and spleen the subpopulation of Tregs was significantly upregulated mainly in EAE remission. Expression of CCR6 on Tregs from the CNS, lymph nodes and spleen was significantly increased during the acute attack of the disease, whereas in the blood this expression was increased during preclinical phase and remission of EAE. Expression of CXCR4 on Tregs from the blood was significantly upregulated in all phases of the disease, but in lymph nodes was increased only during the preclinical phase of EAE. Interestingly, expression of CXCR5 on Tregs from the blood was increased only during the remission of the disease. Moreover, expression of CCR3 on Tregs from lymph nodes was significantly downregulated in all phases of EAE. Conclusion: Presented above observations suggest that some chemokine receptors may be involved in the mechanism of Tregs actions during the development of autoimmune CNS inflammation. PO10-TU-12 Establishment of animal model of experimental autoimmune encephalomyelitis by active immunization
cytes in vitro. Prior neural grafting studies we have to evaluate efficacy of different approaches to induce CNS demyelination. Method: Animals were immunized with spinal cord homogenate in Freund’s adjuvant with Mycobacterium tuberculosis (HFA). Group I of Wistar rats (n = 15) was treated with HFA alone and group II (n = 5) received HFA with octreotide. C57BL6 mice were treated either with HFA plus octreotide (group III, n = 5) or HFA plus Pertussi toxin (group IV, n = 6). Neurological symptoms were recorded for 60 days using a 5-degree scale evaluation scheme. The CNS tissue was examined histologically. Results: In group I, 4 rats showed symptoms of paralysis (reaching score 2 or higher), 3 rats showed symptoms of unsteady gait (score 1.5 or below) and 8 animals remained unaffected. In group II, one animal reached neurologic score 2, two rats had partial loss of tail tonus and one did not show any symptoms at all. After reaching the peak in symptoms, all animals in groups No. I and II recovered spontaneously and no symptoms appeared in later time-points. In group III the onset of disease started later on day 14 but all mice showed symptoms of EAE, 4 mice reached score 1.5 and one reached score 2. In group IV neurological symptoms appeared on day 12 in all mice, 5 animals reached score 2 and one reached score 1.5. In groups III and IV, all animals showed signs of EAE for more than 40 days. The spinal cord of affected animals showed areas of demyelination, cell infiltrates and axonal damage. Conclusion: Augmentation of immune response with octreotide was found to be less effective than sensitisation with Pertussis toxin. Demyelination induced in C57BL6 mice (group IV) followed by Pertussis toxin administration respresents a reliable model of chronic EAE that is suitable for cell transplantation studies. Supported by MSM 0021620820. PO10-TU-13 A prospective study of tumefactive demyelination A. Sen, A. Chaudhuri. Neurology, Queen’s Hospital, Romford, United Kingdom Purpose: Focal neurological symptoms due to large, tumour-like areas of demyelination in brain are well recognised and can affect adults as well as children. There have been few prospective studies of tumefactive demyelination which is usually regarded as a radiological feature of demyelination due to multiple sclerosis. Method: We prospectively followed a cohort of 6 adult patients (F = 4, M = 2) who presented with their first clinical episode of focal neurological deficit due to tumefactive demyelination. None of these patients met Macdonald criteria for the diagnosis of clinically definite multiple sclerosis at presentation. One male patient had MRI abnormalities suggestive of Balo’s concentric sclerosis. In all but 2 patients, the demyelinating lesions were monofocal. In three patients (M = 2, F = 1), lesional brain biopsy was carried out to confirm the diagnosis. Steroid therapy did not significantly influence outcome and only one female patient fulfilled the criteria of multiple sclerosis by temporal dissemination of MRI lesions after follow up period of 18 months, but remained clinically asymptomatic. Conclusion: We propose that tumefactive demyelination is a radiological feature of acute cerebral demyelination and should be considered as a clinically isolated syndrome with benign prognosis in most cases rather than as a definitive precursor of progressive demyelination due to multiple sclerosis. PO10-TU-14 Analysis of acute myelitis in Thai patients
J. Mokry, J. Pazour, D. Cizkova. Histology and Embryology, Charles University Medical Faculty, Hradec Kralove, Czech Republic
C. Laohathai1 , R. Kunnatiranont2 , M. Apiwattanakul1 , T. Tantirittisak1 . 1 Neurology, Prasat Neurological Institute, Bangkok, Thailand; 2 Neuroradiology, Prasat Neurological Institute, Bangkok, Thailand
Purpose: Recently we documented efficacy of differentiation of multipotent neural progenitor cells into functional oligodendro-
Purpose: Relapsing-remitting demyelination of central nervous system in Thai patients most frequently affects optic nerve and
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
PO10-TU-10 A novel free radical scavenger: platinum nanoparticle improves neurological signs and electrophisiological findings in a rat EAE model via quenching ROS and NO H. Yoshida. Dept. of Neurology, Inst. of Neurology, University College London, London, United Kingdom Platinum nanoparticles were prepared by an alcohol reduction method and complementarily stabilized with polyacrilic acid (PAAPt). The average diameter of PAA-Pt was about 2nm. They were well dispersed in water and became colloidal solution. PAA-Pt efficiently quenched superoxide anion (O2 − ), Hydrogen peroxide (H2 O2 ) and Nitric oxide (NO). This quenching activity against ROS and NO persisited like catalysis such as SOD or catalase. Therefore, PAA-Pt may be a useful scavenger which is effective on medical treatment of oxidative stress diseases. In fact, we have shown that platinum nanoparticles are effective on animal models of various ROSrelated diseases like stroke, Alzheimer’s disease, Huntinton disease and so on. And this time, we evaluated the effect of PAA-Pt on experimental autoimmune encephalomyelitis (EAE) using a rat. Intravenous injection of PAA-Pt improves neurological signs and electrophysiological findings in an EAE rat model. PO10-TU-11 Chemokine receptors on regulatory T cells in experimental model of multiple sclerosis A. Glabinski, I. Jatczak, M. Pietruczuk. Medical University of Lodz, Lodz, Poland Purpose: Experimental autoimmune encephalomyelitis (EAE) is a well known animal model of multiple sclerosis (MS), the most common human central nervous system (CNS) demyelinating disease of putative autoimmune pathogenesis. The major goal of this study was to analyze the chemokine receptors expression on regulatory T cells from the CNS, blood, lymph nodes and spleen during different stages of development of EAE. Method: EAE was induced by immunization of female (SJLxSWR)F1 mice with 139–151 PLP peptide. Expression of CCR3, CCR6, CXCR4 and CXCR5 on Tregs was analyzed by flow cytometry in unimmunized control animals, animals with EAE during preclinical phase of the disease, as well as during the acute attack and the disease remission. Results: The number of Tregs in the CNS was constantly increasing during the preclinical phase, acute attack and remission of EAE. In the blood, lymph nodes and spleen the subpopulation of Tregs was significantly upregulated mainly in EAE remission. Expression of CCR6 on Tregs from the CNS, lymph nodes and spleen was significantly increased during the acute attack of the disease, whereas in the blood this expression was increased during preclinical phase and remission of EAE. Expression of CXCR4 on Tregs from the blood was significantly upregulated in all phases of the disease, but in lymph nodes was increased only during the preclinical phase of EAE. Interestingly, expression of CXCR5 on Tregs from the blood was increased only during the remission of the disease. Moreover, expression of CCR3 on Tregs from lymph nodes was significantly downregulated in all phases of EAE. Conclusion: Presented above observations suggest that some chemokine receptors may be involved in the mechanism of Tregs actions during the development of autoimmune CNS inflammation. PO10-TU-12 Establishment of animal model of experimental autoimmune encephalomyelitis by active immunization
cytes in vitro. Prior neural grafting studies we have to evaluate efficacy of different approaches to induce CNS demyelination. Method: Animals were immunized with spinal cord homogenate in Freund’s adjuvant with Mycobacterium tuberculosis (HFA). Group I of Wistar rats (n = 15) was treated with HFA alone and group II (n = 5) received HFA with octreotide. C57BL6 mice were treated either with HFA plus octreotide (group III, n = 5) or HFA plus Pertussi toxin (group IV, n = 6). Neurological symptoms were recorded for 60 days using a 5-degree scale evaluation scheme. The CNS tissue was examined histologically. Results: In group I, 4 rats showed symptoms of paralysis (reaching score 2 or higher), 3 rats showed symptoms of unsteady gait (score 1.5 or below) and 8 animals remained unaffected. In group II, one animal reached neurologic score 2, two rats had partial loss of tail tonus and one did not show any symptoms at all. After reaching the peak in symptoms, all animals in groups No. I and II recovered spontaneously and no symptoms appeared in later time-points. In group III the onset of disease started later on day 14 but all mice showed symptoms of EAE, 4 mice reached score 1.5 and one reached score 2. In group IV neurological symptoms appeared on day 12 in all mice, 5 animals reached score 2 and one reached score 1.5. In groups III and IV, all animals showed signs of EAE for more than 40 days. The spinal cord of affected animals showed areas of demyelination, cell infiltrates and axonal damage. Conclusion: Augmentation of immune response with octreotide was found to be less effective than sensitisation with Pertussis toxin. Demyelination induced in C57BL6 mice (group IV) followed by Pertussis toxin administration respresents a reliable model of chronic EAE that is suitable for cell transplantation studies. Supported by MSM 0021620820. PO10-TU-13 A prospective study of tumefactive demyelination A. Sen, A. Chaudhuri. Neurology, Queen’s Hospital, Romford, United Kingdom Purpose: Focal neurological symptoms due to large, tumour-like areas of demyelination in brain are well recognised and can affect adults as well as children. There have been few prospective studies of tumefactive demyelination which is usually regarded as a radiological feature of demyelination due to multiple sclerosis. Method: We prospectively followed a cohort of 6 adult patients (F = 4, M = 2) who presented with their first clinical episode of focal neurological deficit due to tumefactive demyelination. None of these patients met Macdonald criteria for the diagnosis of clinically definite multiple sclerosis at presentation. One male patient had MRI abnormalities suggestive of Balo’s concentric sclerosis. In all but 2 patients, the demyelinating lesions were monofocal. In three patients (M = 2, F = 1), lesional brain biopsy was carried out to confirm the diagnosis. Steroid therapy did not significantly influence outcome and only one female patient fulfilled the criteria of multiple sclerosis by temporal dissemination of MRI lesions after follow up period of 18 months, but remained clinically asymptomatic. Conclusion: We propose that tumefactive demyelination is a radiological feature of acute cerebral demyelination and should be considered as a clinically isolated syndrome with benign prognosis in most cases rather than as a definitive precursor of progressive demyelination due to multiple sclerosis. PO10-TU-14 Analysis of acute myelitis in Thai patients
J. Mokry, J. Pazour, D. Cizkova. Histology and Embryology, Charles University Medical Faculty, Hradec Kralove, Czech Republic
C. Laohathai1 , R. Kunnatiranont2 , M. Apiwattanakul1 , T. Tantirittisak1 . 1 Neurology, Prasat Neurological Institute, Bangkok, Thailand; 2 Neuroradiology, Prasat Neurological Institute, Bangkok, Thailand
Purpose: Recently we documented efficacy of differentiation of multipotent neural progenitor cells into functional oligodendro-
Purpose: Relapsing-remitting demyelination of central nervous system in Thai patients most frequently affects optic nerve and