Sensorimotor recovery following spinal root axotomy: use of different experimental approaches

• Grant number: 18/05006-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2019
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Ângela Cristina Malheiros Luzo ; Benedito Barraviera ; Cecilia Amelia de Carvalho Zavaglia ; Frank Kirchhoff ; Maria Helena Andrade Santana ; Rui Seabra Ferreira Junior
• Associated research grant(s): 18/17554-2 - Multi-User Equipment approved in grant 2018/05006-0: flow cytometer - ACEA Biosciences model NovoCyte 2060, AP.EMU; 18/14881-2 - Multi-User Equipment approved in grant 2018/05006-0: ultramicrotome Leica UC7, AP.EMU
• Associated scholarship(s): 22/13353-8 - Comparison of the efficacy of 4-Hydroxy-TEMPO and Methylene Blue for the repair of damaged sciatic nerve and assessment of behavioral performance improvement with Neostigmine, BP.MS; 22/05887-2 - Laboratory training program - Laboratory of Nerve Regeneration, BP.TT; 21/02754-9 - Neuroprotective effects of N, N-dimethyltryptamine and FGF-2 after ventral root avulsion and reimplantation with a heterologous fibrin biopolymer, BP.DR; + associated scholarships 21/02727-1 - Biofabrication of nerve guidance conduits, BP.PD; 20/15892-8 - Use of Interferon beta and 4-hydroxy-tempo in the treatment of Amyotrophic Lateral Sclerosis in SOD1G93A mice, BP.DD; 19/06591-7 - Establishment of a model for spinal root reimplantation after avulsion in C57BL/6J mice: use of fibrin polymer and dimethyl-fumarate, BP.MS; 19/02714-7 - Involvement of MHC I, TLR2 and TLR4 in the synaptic plasticity and functional reovery following crushing of spinal ventral roots in mice, BP.PD; 18/25845-7 - Neuroprotective and immunomodulatory effect of dimethyl-fumarate (DMF) after avulsion and reimplantation of spinal motor roots associated to cell-therapy, BP.DD; 19/00833-9 - Laboratory training program - Laboratory of Nerve Regeneration, BP.TT - associated scholarships

Abstract

Motor coordination involves specific neural processes ranging from the perception of stimuli to the achievement of the response, being dependent on delicate sensory-motor integration, which is particularly evident in the spinal cord. Spinal root injuries can lead to motor, sensibility and autonomic losses. This type of lesion constitutes a significant medical problem and usually affects the brachial plexus in consequence of high energy trauma. However, due to the possibility of generating further inflammation and neuropathic pain, surgical procedures do not prioritize the repair of the afferent component. In this context, new therapies need to be developed for dorsal root repair. A promising treatment would be the use of platelet-rich plasma (PRP). Nowadays, PRP is used in a wide range of surgical procedures, and there are several scientific studies demonstrating benefits in treating various types of injuries. Also, immunomodulation and the differential expression of MHC I, TLR2 and 4 seem to interfere in the process of synaptic plasticity following injury. Stem cell therapy has also been used to achieve neuroprotection and to stimulate axonal regrowth. In the present study, we will employ different strategies to repair spinal root injury, evaluating the expression of neurotrophic factors and pro- and anti-inflammatory cytokines. We believe that our results will serve as a basis accelerating nerve regeneration and may contribute to the future clinical use of new therapeutic approaches, fulfilling a critical gap in reparative procedures after this type of injury. (AU)

Scientific publications

(20)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ASSIS, ALEX DIAS; CHIAROTTO, GABRIELA BORTOLANCA; DA SILVA, NATALIA SCANAVACHIA; SIMOES, GUSTAVO FERREIRA; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Pregabalin synchronizes the regeneration of nerve and muscle fibers optimizing the gait recovery of MDX dystrophic mice. FASEB JOURNAL, v. 36, n. 9, p. 21-pg., 2022-09-01. (18/05006-0, 15/14385-7)

HOELZ, AMANDA GARCIA; BERNARDES, DANIELLE; CARTAROZZI, LUCIANA POLITTI; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 16, p. 11-pg., 2022-08-12. (18/05006-0, 15/04665-2, 14/06892-3, 19/02714-7)

CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; FERNANDES, GABRIEL GRIPP; CHIAROTTO, GABRIELA BORTOLANCA; LUZO, ANGELA CRISTINA MALGEIROS; CAMPOS, ALLINE CRISTINA; KIRCHHOFF, FRANK; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. europrotection and gliosis attenuation by intravenous application of human mesenchymal stem cells (hMSC) following ventral root crush in mic. Molecular and Cellular Neuroscience, v. 118, JAN 2022. (18/05006-0, 19/02714-7)

RIBEIRO, PATRICIA; CASTRO, V, MATEUS; PEREZ, MATHEUS; CARTAROZZI, LUCIANA P.; SPEJO, ALINE B.; CHIAROTTO, GABRIELA B.; AUGUSTO, TAIZE M.; OLIVEIRA, ALEXANDRE L. R.. Toll-like receptor 4 (TLR4) influences the glial reaction in the spinal cord and the neural response to injury following peripheral nerve crush. Brain Research Bulletin, v. 155, p. 67-80, FEB 2020. (18/05006-0, 14/06892-3)

CASTRO, MATEUS VIDIGAL DE; SILVA, MONIZE VALERIA RAMOS DA; CHIAROTTO, GABRIELA BORTOLANCA; SANTANA, MARIA HELENA ANDRADE; LUZO, ANGELA CRISTINA MALHEIROS; KYRYLENKO, SERGIY; OLIVEIRA, ALEXANDRE LEITE RODRIGUES DE. Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs). STEM CELLS INTERNATIONAL, v. 2020, OCT 30 2020. (18/05006-0, 15/26206-0)

IGNARRO, RAFFAELA SILVESTRE; BOMBEIRO, ANDRE LUIS; CHIAROTTO, GABRIELA BORTOLANCA; CARTAROZZI, LUCIANA POLITTI; COSER, LILIAN DE OLIVEIRA; GHIZONI, ENRICO; TEDESCHI, HELDER; CENDES, FERNANDO; LOPES-CENDES, ISCIA; ROGERIO, FABIO; et al. Interferon-beta induces major histocompatibility complex of class I (MHC-I) expression and a proinflammatory phenotype in cultivated human astrocytes. DIFFERENTIATION, v. 128, p. 14-pg., 2022-10-25. (17/03619-2, 18/05006-0, 13/07559-3)

DE CASTRO, MATEUS VIDIGAL; RAMOS DA SILVA, MONIZE VALERIA; CHIAROTTO, GABRIELA BORTOLANCA; VOLPE, BRUNO BOSH; SANTANA, MARIA HELENA; MALHEIROS LUZO, ANGELA CRISTINA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Reflex arc recovery after spinal cord dorsal root repair with platelet rich plasma (PRP). Brain Research Bulletin, v. 152, p. 212-224, OCT 2019. (15/26206-0, 18/05006-0, 14/06892-3)

PEREZ, MATHEUS; CARTAROZZI, LUCIANA POLITTI; CHIAROTTO, GABRIELA BORTOLANCA; GUIMARAES, FRANCISCO SILVEIRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy. Neuropharmacology, v. 197, OCT 1 2021. (12/22751-5, 18/05006-0, 19/02714-7)

ASSIS, ALEX DIAS; CHIAROTTO, GABRIELA BORTOLANCA; SIMOES, GUSTAVO FERREIRA; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Pregabalin-induced neuroprotection and gait improvement in dystrophic MDX mice. Molecular and Cellular Neuroscience, v. 114, JUL 2021. (18/05006-0, 15/14385-7)

TOMIYAMA, ANA LAURA M. R.; CARTAROZZI, LUCIANA POLITTI; COSER, LILIANDE OLIVEIRA; CHIAROTTO, GABRIELA BORTOLANCA; OLIVEIRA, ALEXANDRE L. R.. Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1^G93A mice. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 17, p. 20-pg., 2023-08-30. (18/05006-0, 20/15892-8)

MENEZES CARVALHO, NAHANNA ZIMMERMANN; CHIAROTTO, GABRIELA BORTOLANCA; BERNARDES, DANIELLE; GELINSKI KEMPE, PAULA REGINA; RODRIGUES OLIVEIRA, ALEXANDRE LEITE. Neuroprotection by dimethyl fumarate following ventral root crush in C57BL/6J mice. Brain Research Bulletin, v. 164, p. 184-197, NOV 2020. (14/06892-3, 18/05006-0)

LIMA, BRUNO HENRIQUE DE MELO; BOMBEIRO, ANDRE LUIS; CARTAROZZI, LUCIANA POLITTI; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. The Time Course of MHC-I Expression in C57BL/6J and A/J Mice Correlates with the Degree of Retrograde Gliosis in the Spinal Cord following Sciatic Nerve Crush. CELLS, v. 11, n. 23, p. 20-pg., 2022-12-01. (14/06892-3, 18/05006-0)

BOMBEIRO, ANDRE LUIS; DE MELO LIMA, BRUNO HENRIQUE; BONFANTI, AMANDA PIRES; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Improved mouse sciatic nerve regeneration following lymphocyte cell therapy. Molecular Immunology, v. 121, p. 81-91, MAY 2020. (18/05006-0, 14/06892-3)

PAULA R. G. KEMPE; GABRIELA BORTOLANÇA CHIAROTTO; BENEDITO BARRAVIERA; RUI SEABRA FERREIRA JR.; ALEXANDRE L. R. DE OLIVEIRA. Neuroprotection and immunomodulation by dimethyl fumarate and a heterologous fibrin biopolymer after ventral root avulsion and reimplantation. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-05-20. (16/25478-9, 18/25845-7, 18/05006-0)

NATALIA SCANAVACHIA DA SILVA; JULIA LOMBARDI; FRANK KIRCHHOFF; RUI SEABRA FERREIRA JR.; BENEDITO BARRAVIERA; ALEXANDRE LEITE RODRIGUES DE OLIVEIRA; LUCIANA POLITTI CARTAROZZI. Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-05-20. (21/11936-3, 18/05006-0, 22/06609-6, 20/01215-4)

GELINSKI KEMPE, PAULA REGINA; DE CASTRO, MATEUS VIDIGAL; COSER, LILIAN DE OLIVEIRA; CARTAROZZI, LUCIANA POLITTI; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Combination of Adult Mesenchymal Stem Cell Therapy and Immunomodulation with Dimethyl Fumarate Following Spinal Cord Ventral Root Repair. BIOLOGY-BASEL, v. 13, n. 11, p. 18-pg., 2024-11-01. (18/05006-0, 21/11936-3, 18/25845-7)

KEMPE, PAULA REGINA GELINSKI; DE CASTRO, MATEUS VIDIGAL; KHURIYEH, VICTOR CAMPOS; BARRAVIERA, BENEDITO; FERREIRA JR, RUI SEABRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Ultrastructural Evidence of Synapse Preservation and Axonal Regeneration Following Spinal Root Repair with Fibrin Biopolymer and Therapy with Dimethyl Fumarate. POLYMERS, v. 15, n. 15, p. 20-pg., 2023-08-01. (18/05006-0, 21/11936-3, 16/25478-9, 18/25845-7)

BOMBEIRO, ANDRE LUIS; NUNES PEREIRA, BRUNA TOLEDO; BONFANTI, AMANDA PIRES; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Immunomodulation by dimethyl fumarate treatment improves mouse sciatic nerve regeneration. Brain Research Bulletin, v. 160, p. 24-32, JUL 2020. (18/05006-0, 14/06892-3)

CHIAROTTO, GABRIELA BORTOLANCA; CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; BISCOLA, NATALIA PERUSSI; SPEJO, ALINE BARROSO; GUBERT, FERNANDA; FRANCA JUNIOR, MARCONDES; MENDEZ-OTERO, ROSALIA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1(G93A)) of ALS. JOURNAL OF NEUROINFLAMMATION, v. 16, n. 1, NOV 14 2019. (13/16168-8, 17/02895-6, 18/05006-0, 14/06892-3)

CHIAROTTO, GABRIELA BORTOLANCA; CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; TOMIYAMA, ANA LAURA MIDORI ROSSI; DE CASTRO, MATEUS VIDIGAL; DUARTE, ADRIANA S. S.; LUZO, ANGELA CRISTINA MALHEIROS; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Delayed onset, immunomodulation, and lifespan improvement of SOD1G93A mice after intravenous injection of human mesenchymal stem cells derived from adipose tissue. Brain Research Bulletin, v. 186, p. 12-pg., 2022-08-01. (18/05006-0, 13/16168-8)