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Assessment of neuropathic pain and sensorimotor function after stem cell transplantation in animal model of spinal cord injury

Grant number: 15/02154-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2015
Effective date (End): May 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Guilherme Alves Lepski
Grantee:Chary Ely Martin Marquez Batista
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Spinal cord injury is a serious neurological disease that often results in severe loss of motor and sensory function below the level of injury, as well as chronic pain in most patients. It is known that spinal cord injury causes hyper-excitability of specific neurons in the posterior horn of the spinal cord (broad spectrum neurons), which are largely responsible for the myelopathic pain whose delayed onset occurs after the trauma. The possibility of restoration of neurological deficits by cell therapy represents a promising step on the treatment of such injuries, however, the ideal type of stem cell with neurogenic potential as well as the mechanisms responsible for the neurorestoration remains unclear. Thus, the aim of the present work is to clarify the extent to which different types of stem cell are able to generate new neurons in injured spinal cord, the type of connection which is established and the functional repercussion of this intervention in terms of motor recovery and reversal of the chronic neuropathic pain developed after injury. Several protocols for in vitro and in vivo neuronal differentiation preferentially produces GABAergic cells, which in the earlier phase of maturation are excitatory but later become inhibitory. With regard to myelopathic pain, we focus in the hypothesis that inhibitory cells implanted into the system may inhibit pain transmission tonically. To investigate this hypothesis, we plan to use genetically immunodepressed rats which will be anesthetized and submitted to spinal cord contusion using the NYU Impactor (in accordance with the national and international rules governing research on animals). One week after the injury, subgroups of animals will receive transplant of culture medium (medium group) or fetal neural stem cells extracted from E14 embryos of the same species, these being GABAergic precursors derived from telencephalic vesicles (TV group) or Serotoninergic precursors from ventral bulb (VB group). Moreover, a group of animals will be submitted to simulated surgery and implant of culture medium (sham group) and another group will not be submitted to any surgical intervention (control group). The animals will be submitted to specific tests for motor (BBB scale), sensitive (electronic von Frey, Randall and Selitto and Hargreaves) and electrophysiological (motor evoked potential and somatosensory evoked potential) evaluation. After three months, the tested animals will be sacrificed and their spinal cords removed, immunohistochemically stained and analysed under a confocal laser microscope.

Scientific publications
(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)
BATISTA, CHARY M.; MARIANO, ERIC D.; DALE, CAMILA S.; CRISTANTE, ALEXANDRE F.; BRITTO, LUIZ R.; OTOCH, JOSE P.; TEIXEIRA, MANOEL J.; MORGALLA, MATTHIAS; LEPSKI, GUILHERME. Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats. NEURAL REGENERATION RESEARCH, v. 14, n. 11, p. 2011-2019, NOV 2019. Web of Science Citations: 1.
BATISTA, CHARY MARQUEZ; MARIANO, ERIC DOMINGOS; ONUCHIC, FERNANDO; DALE, CAMILA SQUARZONI; DOS SANTOS, GUSTAVO BISPO; CRISTANTE, ALEXANDRE FOGACA; OTOCH, JOSE PINHATA; TEIXEIR, MANOEL JACOBSEN; MORGALLA, MATTHIAS; LEPSKI, GUILHERME. Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat. SOMATOSENSORY AND MOTOR RESEARCH, v. 36, n. 1, p. 14-23, JAN 2 2019. Web of Science Citations: 2.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BATISTA, Chary Ely Martin Marquez. Assessment of neuropathic pain and motor and somatosensory functions after stem cell transplantation in rat spinal cord injury model. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina São Paulo.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.