Phenotypic modifications and quantitative analysis of glial cells in the area of spinal cord injury at the cell-mediated and direct gene delivery gdnf

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On the model of rat spinal cord dosed contusion at T8 level studied the effect of delivery into the area of damage of the cell-mediated and direct gene delivery GDNF on maintaining a population of glial cells. Delivery into the area of damage adenoviral vector with gene GDNF (AdV-gdnf) using human umbilical cord blood mononuclear cells has a greater influence the amount of Ch47+-cells in the ventral horn (VH). Direct delivery of AdV-gdnf influences the amount of Ch47+-cells in dorsal roots entry zone (DREZ). Cell-mediated gene delivery GDNF causes the most pronounced changes in the expression of marker proteins astrocyte GFAP, S100B, and AQP4 in the ventral funiculus (VF) of white matter. Cell-mediated and direct delivery of gene GDNF support population GFAP+/S100B+-cells. The results indicate that the direct and cell-mediated gene delivery GDNF into spinal cord injury have different effects on the populations of glial cells in specific areas of spinal cord, that is important for the optimal method of delivery of therapeutic genes to stimulate posttraumatic neuroregeneration.

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About the authors

Y. O Mukhamedshina

Kazan State Medical University; fazan (Volga region) Federal University

G. F Shaymardanova

Kazan Institute of Biochemistry and Biophysics of RAS

A. R Mukhitov

Kazan Institute of Biochemistry and Biophysics of RAS

E. E Garanina

fazan (Volga region) Federal University

A. A Rizvanov

fazan (Volga region) Federal University

Yu. A Chelyshev

Kazan State Medical University; fazan (Volga region) Federal University


  1. Rowland J.W., Hawryluk G.W., Kwon В. et al. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus. 2008; 25(5): 1-17.
  2. Xu H., Wang J., Zhai Y. et al. Oligodendrocyte and spinal cord injury. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2012; 29(6): 1226-9.
  3. Magnuson D.S., Trinder T.C., Zhang Y.P. et al. Comparing deficits following excitotoxic and contu-sion injuries in the thoracic and lumbar spinal cord of the adult rat. Exp. Neurol. 1999; 156: 191-204.
  4. Rothermundt M., Peters M., Prehn J.H. et al. S100B in brain damage and neurodegeneration. Microsc. Res. Tech. 2003; 60(6): 614-32.
  5. Cheng H., Wu J.P., Tzeng S.F. Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury. J. Neurosci. Res. 2002; 69(3): 397-405.
  6. Airaksinen M.S., Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat. Rev. Neurosci. 2002; 3: 383-94.
  7. Doloff J.C., Waxman D.J. Adenoviral vectors for prodrug activation-based gene therapy for cancer. Anticancer Agents Med. Chem. 2014; 14: 115-26.
  8. Tai M.H., Cheng H., Wu J.P. et al. Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion. Exp. Neurol. 2003; 183(2): 508-15.
  9. Tang X.Q., Wang Y., Huang Z.H. et al. Adenovirus-mediated delivery of GDNF ameliorates corticospinal neuronal atrophy and motor function deficits in rats with spinal cord injury. Neuroreport 2004; 15(3): 425-9.
  10. Degeorge M.L., Marlowe D., Werner E. et al. Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury. Brain Res. 2011; 27(1403): 45-56.
  11. Scheff S.W., Rabchevsky A.G., Fugaccia I. et al. Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma 2003; 20(2): 179-93.
  12. Rizvanov A.A., Kiyasov A.P., Gaziziov I.M. et al. Human umbilical cord blood cells transfected with VEGF and L(1)CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neurotrophic factors to support neurogenesisa novel approach in stem cell therapy. Neurochem. Int. 2008; 53(6-8): 389-94. (Приволжского) федерального университета среди ведущих мировых научно-образовательных центров. Работа частично выполнена на оборудовании Междисциплинарного центра коллективного пользования и Научно образовательного центра фармацевтики Казанского (Приволжского) федерального университета.
  13. Черенкова е.е., Федотова М.А., Борисов Р.Р. и др. Создание рекомбинантных аденовирусов и лентивирусов, экспрессирующих ангиогенные и нейропротекторные факторы, с помощью технологии клонирования Gateway. Ж. Клеточная трансплантология и тканевая инженерия 2012; 7(3): 164-8.
  14. Мухамедшина Я.О., Шаймарданова Г.Ф., Салафутдинов И.И. и др. Доставка рекомбинантного аденовируса с клонированным геном GDNF в область травмы спинного мозга при помощи клеток крови пуповины человека стимулирует восстановление двигательной функции и поддерживает популяцию глиальных клеток. Клеточная трансплантология и тканевая инженерия 2013; 8(3): 129-32.
  15. Odermatt B., Wellershaus K., Wallraff A. et al. Connexin 47 (Cx47)-deficient mice with enhanced green fluorescent protein reporter gene reveal predominant oligodendrocytic expression of Cx47 and display vacuolized myelin in the CNS. J. Neurosci. 2003; 23(11): 4549-59.
  16. Martinez L., Sonsoles de Lacalle. Astrocytic reaction to a lesion, under hormonal deprivation. Neurosci. Lett. 2007; 415(2): 190-3.
  17. Pisani F., Rossi A., Nicchia G.P. et al. Translational regulation mechanisms of aquaporin-4 supramolecular organization in astrocytes. Glia 2011; 59: 1923-32.
  18. Donato R., Cannon B.R., Sorci G. et al. Functions of S100 proteins. Curr. Mol. Med. 2013; 13: 24-57.
  19. Мухамедшина Я.О. Посттравматические реакции спинного мозга крысы при трансплантации мононуклеарных клеток крови пуповины человека, трансфицированных плазмидой pBud VEGF FGF2 [диссертация]. Саранск: Мордовский государственный университет имени Н.П. Огарёва; 2013.
  20. Lepore A.C., O'Donnell J., Kim A.S. et al. Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury. Glia 2011; 59(12): 1996-2005.
  21. Iwase T., Jung C.G., Bae H. et al. Glial cell line-derived neurotrophic factor-induced signal-ing in Schwann cells. J. Neurochem. 2005; 94(6): 1488-99.
  22. Jessen R.K., Mirsky R. The origin and development of glial cells in peripheral nerves. Neuroscience 2005; 6: 671-82.
  23. Chen C.T., Foo N.H., Liu W.S. Infusion of human umbilical cord blood cells ameliorates hind limb dysfunction in experimental spinal cord injury through anti-inflammatory, vasculogenic and neurotrophic mechanisms. Pediatr. Neonatol. 2008; 49(3): 77-83.

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