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Conference Paper: Memantine and pioglitazone ameliorate motor impairments and complement-independent cord pathologies in mice received aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder (NMOSD) patients

TitleMemantine and pioglitazone ameliorate motor impairments and complement-independent cord pathologies in mice received aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder (NMOSD) patients
Authors
Issue Date2018
PublisherSage Publications Ltd. The Journal's web site is located at http://msj.sagepub.com/
Citation
The 11th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) 2018, Sydney, Australia, 1-3 November 2018. In Multiple Sclerosis Journal, 2018, v. 25 n. 3, p. 440-441 How to Cite?
AbstractBackground: NMOSD are predominantly autoimmune astrocytopathy characterized by recurrent attacks of CNS inflammation. Binding of aquaporin-4 autoantibodies (AQP4-IgG) to astrocytic AQP4 triggers neuroinflammation. We reported AQP4-IgG induced motor impairments associated with complement-independent astrocytic injury, glutamate transporter (EAAT2) loss, microglial/macrophage activation, demyelination and axonal injury in mice with breached blood-brain-barrier (BBB); suggesting a role of glutamate excitotoxicity and microglial/macrophage activation in NMOSD pathophysiologies. Objective: To examine whether memantine (NMDA receptor antagonist) and pioglitazone (peroxisome proliferatoractivated receptor-γ agonist) can attenuate motor impairments and pathologies in mice received AQP4-IgG. Methods: After breaching BBB with bacterial proteins, mice received daily intraperitoneal injections of IgG purified from AQP4-IgG-seropositive NMOSD patients [IgG(AQP4+)] or healthy individuals as control for 8 days. IgG(AQP4+) mice received daily oral gavage of vehicle, or 60 mg/kg memantine or 80 mg/kg pioglitazone. Motor functions were assessed by beam walking test. Spinal cords were collected for immunofluorescence analysis. Results: Vehicle-treated IgG(AQP4+) mice required longer time with more paw slips to walk across narrow beams than sham. Memantine and pioglitazone significantly reduced the time and number of paw slips of IgG(AQP4+) mice compared with vehicle (p<0.01), suggesting motor function improvement. Neither memantine nor pioglitazone reduced aquaporin-4 loss in spinal cord of IgG(AQP4+) mice compared with vehicle. Importantly, memantine and pioglitazone significantly reduced glial fibrillary acidic protein loss (p<0.05), microglial/ macrophage activation (p<0.001), demyelination (p<0.001) and axonal loss (p<0.05) in IgG(AQP4+) mice compared with vehicle, suggesting an improvement of IgG(AQP4+)-induced complement-independent pathologies. Conclusion: Memantine and pioglitazone have therapeutic potentials for ameliorating severity of NMOSD attack.
DescriptionTwo Minute Oral Presentation of Selected Posters - no. O-11
Persistent Identifierhttp://hdl.handle.net/10722/275306
ISSN
2017 Impact Factor: 5.28
2015 SCImago Journal Rankings: 2.177

 

DC FieldValueLanguage
dc.contributor.authorChan, KH-
dc.contributor.authorYick, LW-
dc.date.accessioned2019-09-10T02:39:52Z-
dc.date.available2019-09-10T02:39:52Z-
dc.date.issued2018-
dc.identifier.citationThe 11th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) 2018, Sydney, Australia, 1-3 November 2018. In Multiple Sclerosis Journal, 2018, v. 25 n. 3, p. 440-441-
dc.identifier.issn1352-4585-
dc.identifier.urihttp://hdl.handle.net/10722/275306-
dc.descriptionTwo Minute Oral Presentation of Selected Posters - no. O-11-
dc.description.abstractBackground: NMOSD are predominantly autoimmune astrocytopathy characterized by recurrent attacks of CNS inflammation. Binding of aquaporin-4 autoantibodies (AQP4-IgG) to astrocytic AQP4 triggers neuroinflammation. We reported AQP4-IgG induced motor impairments associated with complement-independent astrocytic injury, glutamate transporter (EAAT2) loss, microglial/macrophage activation, demyelination and axonal injury in mice with breached blood-brain-barrier (BBB); suggesting a role of glutamate excitotoxicity and microglial/macrophage activation in NMOSD pathophysiologies. Objective: To examine whether memantine (NMDA receptor antagonist) and pioglitazone (peroxisome proliferatoractivated receptor-γ agonist) can attenuate motor impairments and pathologies in mice received AQP4-IgG. Methods: After breaching BBB with bacterial proteins, mice received daily intraperitoneal injections of IgG purified from AQP4-IgG-seropositive NMOSD patients [IgG(AQP4+)] or healthy individuals as control for 8 days. IgG(AQP4+) mice received daily oral gavage of vehicle, or 60 mg/kg memantine or 80 mg/kg pioglitazone. Motor functions were assessed by beam walking test. Spinal cords were collected for immunofluorescence analysis. Results: Vehicle-treated IgG(AQP4+) mice required longer time with more paw slips to walk across narrow beams than sham. Memantine and pioglitazone significantly reduced the time and number of paw slips of IgG(AQP4+) mice compared with vehicle (p<0.01), suggesting motor function improvement. Neither memantine nor pioglitazone reduced aquaporin-4 loss in spinal cord of IgG(AQP4+) mice compared with vehicle. Importantly, memantine and pioglitazone significantly reduced glial fibrillary acidic protein loss (p<0.05), microglial/ macrophage activation (p<0.001), demyelination (p<0.001) and axonal loss (p<0.05) in IgG(AQP4+) mice compared with vehicle, suggesting an improvement of IgG(AQP4+)-induced complement-independent pathologies. Conclusion: Memantine and pioglitazone have therapeutic potentials for ameliorating severity of NMOSD attack.-
dc.languageeng-
dc.publisherSage Publications Ltd. The Journal's web site is located at http://msj.sagepub.com/-
dc.relation.ispartofMultiple Sclerosis Journal-
dc.relation.ispartof11th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) 2018-
dc.rightsMultiple Sclerosis Journal. Copyright © Sage Publications Ltd.-
dc.titleMemantine and pioglitazone ameliorate motor impairments and complement-independent cord pathologies in mice received aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder (NMOSD) patients-
dc.typeConference_Paper-
dc.identifier.emailChan, KH: koonho@hku.hk-
dc.identifier.emailYick, LW: lwyick@hku.hk-
dc.identifier.authorityChan, KH=rp00537-
dc.identifier.hkuros302683-
dc.identifier.volume25-
dc.identifier.issue3-
dc.identifier.spage440-
dc.identifier.epage441-
dc.publisher.placeUnited Kingdom-

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