Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats
Autor: | Eric Domingos Mariano, Manoel Jacobsen Teixeira, Guilherme Lepski, Luiz R.G. Britto, Camila Squarzoni Dale, Chary Marquez Batista, Alexandre Fogaça Cristante, José Pinhata Otoch, Matthias Morgalla |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
serotoninergic neuron Stereology spinal cord injuries chronic pain neural stem cells cell transplantation neuronal differentiation GABAergic neuron enkephalinergic neuron lcsh:RC346-429 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience medicine Spinal cord injury lcsh:Neurology. Diseases of the nervous system biology business.industry Chronic pain medicine.disease Spinal cord Neural stem cell Transplantation 030104 developmental biology medicine.anatomical_structure Anesthesia Neuropathic pain biology.protein NeuN business 030217 neurology & neurosurgery Research Article |
Zdroj: | Neural Regeneration Research, Vol 14, Iss 11, Pp 2011-2019 (2019) Neural Regeneration Research |
ISSN: | 1673-5374 |
Popis: | 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 ~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 São Paulo (protocol number 033/14) on March 4, 2016. |
Databáze: | OpenAIRE |
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