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Pain inhibition through transplantation of.f.tal neuronal progenitors into the injured spinal cord in rats

Neural Regeneration Research 2019年第11期14卷 2011-2019页

作者： Chary M. Batista Eric D. Mariano Camila S. Dale alexandre f. cristante Luiz R. Britto Jose P. Otoch Manoel J. Teixeira Matthias Morgalla Guilherme Lepski Department of.Neurology School of MedicineUniversity of Sao PauloSao PauloBrazil Department of.Anatomy Institute of Biomedical ScienceUniversity of Sao PauloSao PauloBrazil Department of.Orthopedic and Traumatology School of MedicineUniversity of Sao PauloSao PauloBrazil Department of.Physiology and Biophysics Institute of Biomedical ScienceUniversity of Sao PauloSao PauloBrazil Department of.Surgery School of MedicineUniversity of Sao PauloSao PauloBrazil Department of.Neurosurgery Eberhard-Karls UniversityTuebingenGermany Department of.Psychiatry School of MedicineUniversity of Sao PauloSao PauloBrazil

Neuropathic pain af.er 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 ef.ectiveness against pain remains largely controversial. Here, we evaluated the ability of.f.tal neural stem cells(f.SC) to relieve chronic pain and, secondarily, their ef.ects on motor recovery. Adult Wistar rats with traumatic SCI were treated, 10 days af.er injury, with intra-spinal injections of.culture medium(sham) or f.SCs extracted f.om telencephalic vesicles(TV group) or the ventral medulla(VM group) of.E/14 embryos. Sensory(von f.ey f.laments and hot plate) and motor(the Basso, Beattie,Bresnahan locomotor rating scale and inclined plane test) assessments were perf.rmed during 8 weeks. Thereaf.er, spinal cords were processed f.r immunof.uorescence and transplanted cells were quantif.ed by stereology. The results showed improvement of.thermal hyperalgesia in the TV and VM groups at 4 and 5 weeks af.er transplantation, respectively. Moreover, mechanical allodynia improved in both the TV and VM groups at 8 weeks. No signif.cant motor recovery was observed in the TV or VM groups compared with sham. Stereological analyses showed that ~70% of.TV and VM cells dif.erentiated 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 f.om TV and VM, once implanted into the injured spinal cord, maturate into dif.erent neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and all subtypes alleviate pain, despite no signif.cant motor recovery. The study was approved by the Animal Ethics Committee of.the Medical School of.the University of.S?o Paulo(protocol number 033/14) on March 4, 2016.

关键词： spinal cord injuries chronic pain neural stem cells cell transplantation neuronal dif.erentiation GABAergic neuron serotoninergic neuron enkephalinergic neuron

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