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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
Title | Memantine and pioglitazone ameliorate motor impairments and complement-independent cord pathologies in mice received aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder (NMOSD) patients |
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Authors | |
Issue Date | 2018 |
Publisher | Sage 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? |
Abstract | Background: 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. |
Description | Two Minute Oral Presentation of Selected Posters - no. O-11 |
Persistent Identifier | http://hdl.handle.net/10722/275306 |
ISSN | 2023 Impact Factor: 4.8 2023 SCImago Journal Rankings: 1.901 |
DC Field | Value | Language |
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dc.contributor.author | Chan, KH | - |
dc.contributor.author | Yick, LW | - |
dc.date.accessioned | 2019-09-10T02:39:52Z | - |
dc.date.available | 2019-09-10T02:39:52Z | - |
dc.date.issued | 2018 | - |
dc.identifier.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 | - |
dc.identifier.issn | 1352-4585 | - |
dc.identifier.uri | http://hdl.handle.net/10722/275306 | - |
dc.description | Two Minute Oral Presentation of Selected Posters - no. O-11 | - |
dc.description.abstract | Background: 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.language | eng | - |
dc.publisher | Sage Publications Ltd. The Journal's web site is located at http://msj.sagepub.com/ | - |
dc.relation.ispartof | Multiple Sclerosis Journal | - |
dc.relation.ispartof | 11th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS) 2018 | - |
dc.rights | Multiple Sclerosis Journal. Copyright © Sage Publications Ltd. | - |
dc.title | Memantine and pioglitazone ameliorate motor impairments and complement-independent cord pathologies in mice received aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder (NMOSD) patients | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Chan, KH: koonho@hku.hk | - |
dc.identifier.email | Yick, LW: lwyick@hku.hk | - |
dc.identifier.authority | Chan, KH=rp00537 | - |
dc.identifier.hkuros | 302683 | - |
dc.identifier.volume | 25 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 440 | - |
dc.identifier.epage | 441 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1352-4585 | - |