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The effects of BMSCs transplantation on autophagy by CX43 in the hippocampus following traumatic brain injury in rats

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Abstract

Traumatic brain injury (TBI) can initiate a series of complicated pathological events, and induce various types of neuronal cell death including autophagy and apoptosis. Currently, the treatment of TBI is one of the main challenges in neurobiology. In this regard, the administration of bone marrow stromal cells (BMSCs) represents a novel treatment modality for TBI. However, the protective mechanism of BMSCs was unknown in the TBI. The aim of the present study was to assess the effects of BMSCs on connexin 43(CX43) and autophagy in the hippocampus following TBI in rats. A rat model of TBI was created using a modified weight-drop device. Double-membrane structures in the process of autophagy formation were frequently observed in injured brain by electron microscopy. The levels of autophagic pathway associated proteins and CX43 were also detected by western blot analysis. Specifically, immunoblotting results showed that BMSCs treatment after TBI could down-regulate light chain 3 (LC3), Beclin-1 and CX43 expression in the hippocampus. Taken together, our results demonstrated that BMSCs were able to significantly suppress TBI-induced autophagy activity, and the potential mechanism by regulating CX43 levels.

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Abbreviations

CX43:

Connexin 43

BMSCs:

Bone marrow stromal cells

CNS:

Central nervous system

LC3:

Light chain 3

NeuN:

Neuronal nuclei

PBS:

Phosphate-buffered saline

TBI:

Traumatic brain injury

References

  1. Zhang M, Shan H, Gu Z, Wang D, Wang T, Wang Z, Tao L (2012) Increased expression of calcium/calmodulin-dependent protein kinase type II subunit delta after rat traumatic brain injury. J Mol Neurosci 46(3):631–643

    Article  CAS  PubMed  Google Scholar 

  2. Clark RS, Bay H, Chu CT, Alber SM, Kochanek PM, Watkins SC (2008) Autophagy is increased in mice after traumatic brain injury and is detectable in human brain after trauma and critical illness. Autophagy 4(1):88–90

    CAS  PubMed  Google Scholar 

  3. Sadasivan S, Dunn WA Jr, Hayes RL, Wang KK (2008) Changes in autophagy proteins in a rat model of controlled cortical impact induced brain injury. Biochem Biophys Res Commun 373(4):478–481

    Article  CAS  PubMed  Google Scholar 

  4. Wang T, Zhang L, Zhang M, Bao H, Liu W, Wang Y, Wang L, Dai D, Chang P, Dong W (2012) [Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice. Neuroscience 231:70–81

    Article  PubMed  Google Scholar 

  5. Lai Y, Hickey RW, Yaming Chen HB (2007) Autophagy is increased after traumatic brain injury in mice and is partially inhibited by the antioxidant γ-glutamylcysteinyl ethyl ester. J Cereb Blood Flow Metab 28(3):540–550

    Article  PubMed  Google Scholar 

  6. Luo C-L, Li B-X, Chen X-P, Sun Y-X, Bao H-J, Dai D-K, Shen Y-W, Xu H-F, Ni H, Wan L (2011) Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience 184:54–63

    Article  CAS  PubMed  Google Scholar 

  7. Mahmood A, Lu D, Qu C, Goussev A, Chopp M (2007) Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats. Neurosurgery 60(3):546–554

    Article  PubMed  Google Scholar 

  8. Osanai T, Kuroda S, Sugiyama T, Kawabori M, Ito M, Shichinohe H, Kuge Y, Houkin K, Tamaki N, Iwasaki Y (2012) Therapeutic effects of intra-arterial delivery of bone marrow stromal cells in traumatic brain injury of rats—in vivo cell tracking study by near-infrared fluorescence imaging. Neurosurgery 70(2):435–444

    Article  PubMed  Google Scholar 

  9. Marmarou A, Foda MAA-E, Brink Wvd, Campbell J, Kita H, Demetriadou K (1994) A new model of diffuse brain injury in rats: Part I: Pathophysiology and biomechanics. J Neurosurg 80(2):291–300

    Article  CAS  PubMed  Google Scholar 

  10. Bakhtiary M, Marzban M, Mehdizadeh M, Joghataei MT, Khoei S, Laribi B, Tondar M, Moshkforoush A (2010) Comparison of transplantation of bone marrow stromal cells (BMSC) and stem cell mobilization by granulocyte colony stimulating factor after traumatic brain injury in rat. Iranian Biomed J 14(4):142–149

    Google Scholar 

  11. Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36(12):2491–2502

    Article  CAS  PubMed  Google Scholar 

  12. Kuroda S, Shichinohe H, Houkin K, Iwasaki Y (2011) Autologous bone marrow stromal cell transplantation for central nervous system disorders—recent progress and perspective for clinical application. J Stem Cell Regen Med 7(1):2–13

    Google Scholar 

  13. Mahmood A, Goussev A, Lu D, Qu C, Xiong Y, Kazmi H, Chopp M (2008) Long-lasting benefits after treatment of traumatic brain injury (TBI) in rats with combination therapy of marrow stromal cells (MSCs) and simvastatin. J Neurotrauma 25(12):1441–1447

    Article  PubMed Central  PubMed  Google Scholar 

  14. Björklund LM, Sánchez-Pernaute R, Chung S, Andersson T, Chen IYC, McNaught KSP, Brownell A-L, Jenkins BG, Wahlestedt C, Kim K-S (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci 99(4):2344–2349

    Article  PubMed Central  PubMed  Google Scholar 

  15. Bonilla C, Zurita M, Otero L, Aguayo C, Vaquero J (2009) Delayed intralesional transplantation of bone marrow stromal cells increases endogenous neurogenesis and promotes functional recovery after severe traumatic brain injury. Brain Inj 23(9):760–769

    Article  PubMed  Google Scholar 

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Acknowledgments

The present study was supported by a grant from the Natural Science Foundation of Hebei Province (No. H2012401071).

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The authors declare that they have no conflict of interest.

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Correspondence to Liqian Sun.

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Sun, L., Gao, J., Zhao, M. et al. The effects of BMSCs transplantation on autophagy by CX43 in the hippocampus following traumatic brain injury in rats. Neurol Sci 35, 677–682 (2014). https://doi.org/10.1007/s10072-013-1575-6

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  • DOI: https://doi.org/10.1007/s10072-013-1575-6

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