Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats

Autor(es)

Batista, Chary M. ^[1] ; Mariano, Eric D. ^[1] ; Dale, Camila S. ^[2] ; Cristante, Alexandre F. ^[3] ; Britto, Luiz R. ^[4] ; Otoch, Jose P. ^[5] ; Teixeira, Manoel J. ^[1] ; Morgalla, Matthias ^[6] ; Lepski, Guilherme ^{[7, 6]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Neurol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Orthoped & Traumatol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med, Dept Surg, Sao Paulo - Brazil

^[6] Eberhard Karls Univ Tubingen, Dept Neurosurg, Tubingen - Germany

^[7] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEURAL REGENERATION RESEARCH; v. 14, n. 11, p. 2011-2019, NOV 2019.
• Citações Web of Science: 0

Resumo

Neuropathic pain after spinal cord injury (SCI) is a complex condition that responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Here, we evaluated the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, their effects on motor recovery. Adult Wistar rats with traumatic SCI were treated, 10 days after injury, with intra-spinal injections of culture medium (sham) or fNSCs extracted from telencephalic vesicles (TV group) or the ventral medulla (VM group) of E/14 embryos. Sensory (von Frey filaments and hot plate) and motor (the Basso, Beattie, Bresnahan locomotor rating scale and inclined plane test) assessments were performed during 8 weeks. Thereafter, spinal cords were processed for immunofluorescence and transplanted cells were quantified by stereology. The results showed improvement of thermal hyperalgesia in the TV and VM groups at 4 and 5 weeks after transplantation, respectively. Moreover, mechanical allodynia improved in both the TV and VM groups at 8 weeks. No significant motor recovery was observed in the TV or VM groups compared with sham. Stereological analyses showed that similar to 70% of TV and VM cells differentiated into NeuN(+) neurons, with a high proportion of enkephalinergic and GABAergic cells in the TV group and enkephalinergic and serotoninergic cells in the VM group. Our study suggests that neuronal precursors from TV and VM, once implanted into the injured spinal cord, maturate into different neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and all subtypes alleviate pain, despite no significant motor recovery. The study was approved by the Animal Ethics Committee of the Medical School of the University of Sao Paulo (protocol number 033/14) on March 4, 2016. (AU)

• Processo FAPESP: 13/12056-0 - Tratamento da dor mielopática por meio de transplante de progenitores neurais em modelo de lesão medular em ratos
• Beneficiário: Guilherme Alves Lepski
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/02154-0 - Avaliação da dor neuropática e das funções motora e somato-sensitiva após o transplante de células-tronco em modelo de lesão da medula espinal em ratos
• Beneficiário: Chary Ely Martin Marquez Batista
• Linha de fomento: Bolsas no Brasil - Doutorado