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Evaluation of PTEN Inhibitor Following Spinal Cord Injury on Recovery of Voiding Efficiency and Motor Function Observed by Regeneration in Spinal Cord

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Purpose: Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Therefore, we investigated the effects of a tissue gene nerve (TGN), PTEN inhibitor, on voiding function, motor function, and the expression of growth factors after SCI. Methods: In this experiment, female rats were randomly divided into 3 groups (n=10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and TGN-treated group. Cystometry; the Basso, Beattie, and Bresnahan (BBB) scale test; the ladder walking test; hematoxylin and eosin staining; and Western blotting for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) were performed to evaluate functional and molecular changes. Results: After SCI, the rats exhibited decreased walking ability according to the BBB scale test and impaired coordinative function according to the ladder walking test. The PTEN inhibitor promoted enhanced walking ability and coordinative function. Cystometry showed voiding impairment after SCI and improved voiding function was observed after PTEN treatment. Overexpression of VEGF, BDNF, and NGF were observed after SCI. Administration of PTEN inhibitors significantly attenuated the overexpression of growth factors due to SCI. Conclusion: PTEN inhibitor treatment diminished the overexpression of growth factors and promoted the repair of damaged tissue. PTEN inhibitor-treated rats also showed improved motor function and improved voiding function. Therefore, we suggest TGN as a new therapeutic agent that can be applied after SCI.

Abstract

Purpose: Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Therefore, we investigated the effects of a tissue gene nerve (TGN), PTEN inhibitor, on voiding function, motor function, and the expression of growth factors after SCI. Methods: In this experiment, female rats were randomly divided into 3 groups (n=10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and TGN-treated group. Cystometry; the Basso, Beattie, and Bresnahan (BBB) scale test; the ladder walking test; hematoxylin and eosin staining; and Western blotting for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) were performed to evaluate functional and molecular changes. Results: After SCI, the rats exhibited decreased walking ability according to the BBB scale test and impaired coordinative function according to the ladder walking test. The PTEN inhibitor promoted enhanced walking ability and coordinative function. Cystometry showed voiding impairment after SCI and improved voiding function was observed after PTEN treatment. Overexpression of VEGF, BDNF, and NGF were observed after SCI. Administration of PTEN inhibitors significantly attenuated the overexpression of growth factors due to SCI. Conclusion: PTEN inhibitor treatment diminished the overexpression of growth factors and promoted the repair of damaged tissue. PTEN inhibitor-treated rats also showed improved motor function and improved voiding function. Therefore, we suggest TGN as a new therapeutic agent that can be applied after SCI.

참고문헌 (25)

  1. McDonald JW, "Spinal-cord injury", Lancet, 359, pp.417~425 (2002)
  2. Witiw CD, "Acute spinal cord injury", J Spinal Disord Tech, 28, pp.202~210 (2015)
  3. Fakhoury M, "Spinal cord injury : overview of experimental approaches used to restore locomotor activity", Rev Neurosci, 26, pp.397~405 (2015)
  4. 정성진, "The Current Positioning of Augmentation Enterocystoplasty in the Treatment for Neurogenic Bladder", International Neurourology Journal, 24(3), pp.200~210 (2020), 대한배뇨장애요실금학회[DOI]
  5. Nseyo U, "Long-term complications of the neurogenic bladder", Urol Clin North Am, 44, pp.355~366 (2017)
  6. Bragge P, "A systematic review of the content and quality of clinical practice guidelines for management of the neurogenic bladder following spinal cord injury", Spinal Cord, 57, pp.540~549 (2019)
  7. 김수진, "Stem Cell Therapy for Neurogenic Bladder After Spinal Cord Injury: Clinically Possible?", International Neurourology Journal, 24, pp.3~10 (2020), 대한배뇨장애요실금학회[DOI]
  8. Cho YS, "Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats", J Biomed Sci, 21, pp.43~ (2014)
  9. Hanieh Salehi-Pourmehr, "Stem Cell Therapy for Neurogenic Bladder Dysfunction in Rodent Models: A Systematic Review", International Neurourology Journal, 24(3), pp.241~257 (2020), 대한배뇨장애요실금학회[DOI]
  10. Christie KJ, "PTEN inhibition to facilitate intrinsic regenerative outgrowth of adult peripheral axons", J Neurosci, 30, pp.9306~9315 (2010)
  11. Zhao J, "PTEN inhibition prevents rat cortical neuron injury after hypoxia-ischemia", Neuroscience, 238, pp.242~251 (2013)
  12. 김유미, "Combination of treadmill exercise with bone marrow stromal cells transplantation activates protein synthesis-related molecules in soleus muscle of the spinal cord injured rats", Journal of exercise rehabilitation, 15(3), pp.377~382 (2019), 한국운동재활학회[DOI]
  13. Basso DM, "A sensitive and reliable locomotor rating scale for open field testing in rats", J Neurotrauma, 12, pp.1~21 (1995)
  14. Schira J, "Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood", Brain, 135, pp.431~446 (2012)
  15. 고일규, "Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats", International Neurourology Journal, 22(1), pp.20~29 (2018), 대한배뇨장애요실금학회
  16. 김유미, "Treadmill exercise with bone marrow stromal cells transplantation facilitates neuroprotective effect through BDNF-ERK1", 2 pathway in spinal cord injury rats, 2018, pp.14(3), 335~340[DOI]
  17. 임효선, "Therapeutic Potential of Human Turbinate-Derived Mesenchymal Stem Cells in Experimental Acute Ischemic Stroke", International Neurourology Journal, 22, pp.131~138 (2018), 대한배뇨장애요실금학회
  18. 이수신, "Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils", Journal of exercise rehabilitation, 16(1), pp.49~57 (2020), 한국운동재활학회[DOI]
  19. Park KK, "Promoting axon regeneration in the adult CNS by modulation of the PTEN", mTOR pathway, 2008, pp.322, 963~966
  20. Liu K, "PTEN deletion enhances the regenerative ability of adult corticospinal neurons", Nat Neurosci, 13, pp.1075~1081 (2010)
  21. Ohtake Y, "PTEN inhibition and axon regeneration and neural repair", Neural Regen Res, 10, pp.1363~1368 (2015)
  22. Walker CL, "Systemic bisperoxovanadium activates Akt", mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury, 2012, pp.7, e30012~
  23. Mao L, "Delayed administration of a PTEN inhibitor BPV improves functional recovery after experimental stroke", Neuroscience, 231, pp.272~281 (2013)
  24. Wu H, "Simvastatin-mediated upregulation of VEGF and BDNF, activation of the PI3K", Akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury, 2008, pp.25, 130~139
  25. Sang Q, "NGF and PI3K", Akt signaling participate in the ventral motor neuronal protection of curcumin in sciatic nerve injury rat models, 2018, pp.103, 1146~1153

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