{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:45:06Z","timestamp":1789584306875,"version":"build-2803163510"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202404000-00035\/inline-graphic1\/v\/2023-09-09T133047Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    Anti-ganglioside antibodies are associated with delayed\/poor clinical recovery in Guillain-Barr\u00e8 syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA\/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon regeneration of peripheral nerves, where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers. Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632. Treatment with a total dosage of 9 mg\/kg of Y-27632 resulted in a complete prevention of anti-GD1a\/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity. In contrast, the same dose showed toxic effects on the regeneration of myelinated fibers. Interestingly, scale down of the dosage of Y-27632 to 5 mg\/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a\/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632. Overall, these findings confirm the\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    participation of RhoA\/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a\/GT1b monoclonal antibody. Our findings open the possibility of therapeutic pharmacological intervention targeting RhoA\/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.382258","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T11:01:17Z","timestamp":1694257277000},"page":"895-899","source":"Crossref","is-referenced-by-count":7,"title":["Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies"],"prefix":"10.4103","volume":"19","author":[{"given":"Andr\u00e9s","family":"Berardo","sequence":"first","affiliation":[{"name":"Laboratorio de Neurobiolog\u00eda, Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Martin Ferreyra, (INIMEC)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)-Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian R.","family":"Bacaglio","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurobiolog\u00eda, Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Martin Ferreyra, (INIMEC)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)-Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"},{"name":"Departamento de Qu\u00edmica Biol\u00f3gica-Centro de Investigaciones en Qu\u00edmica Biol\u00f3gica de C\u00f3rdoba (CIQUIBIC)- Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Cs. Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara B.","family":"B\u00e1ez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurobiolog\u00eda, Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Martin Ferreyra, (INIMEC)-Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)-Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"},{"name":"Departamento de Qu\u00edmica Biol\u00f3gica-Centro de Investigaciones en Qu\u00edmica Biol\u00f3gica de C\u00f3rdoba (CIQUIBIC)- Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Cs. Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Sambuelli","sequence":"additional","affiliation":[{"name":"Servicio de Anatom\u00eda Patol\u00f3gica, Cl\u00ednica Universitaria Reina Fabiola, Universidad Cat\u00f3lica de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2263-1500","authenticated-orcid":false,"given":"Kazim A.","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Medical School at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-6792","authenticated-orcid":false,"given":"Pablo H. 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