Skip to main content
SpringerLink
Log in

Transplantation of Olfactory Ensheathing Cells Attenuates Acute Carbon Monoxide Poisoning-Induced Brain Damages in Rats

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

In this study, the therapeutic effect of olfactory ensheathing cells (OEC) transplantation on brain damage was evaluated on acute carbon monoxide (CO) poisoning rat model. Two weeks after primary culture, OECs were microinjected into hippocampus of CO poisoning rats. Survival of OECs in the host was observed and quantified. OECs survived at 2 weeks, but surviving cell number was found sharply decreased at 6 weeks and reduced to less than 103 at 8 weeks after transplantation. At 2 weeks after transplantation, motor function test and cerebral edema assay were performed and followed by pathological examination including hematoxylin and eosin and immunohistochemistry staining to observe the neuron injury and synapsin I and growth associated protein-43 (GAP-43) expression. Furthermore, biomarkers of oxidative stress and apoptosis related proteins in the hippocampus were detected. The results showed that CO exposure led to neurological dysfunction and cerebral edema in rats. After OEC transplantation, neurological function was significantly improved and the cerebral edema was alleviated. In addition, the numbers of neurons and Nissl bodies were increased and synapsin I and GAP-43 protein expressions were upregulated in the hippocampus. Compared with CO poisoned rats, superoxide dismutase activity and glutathione content were both increased and methane dicarboxylic aldehyde level was decreased in the hippocampus of OEC transplanted rats. Moreover, OEC transplantation reduced apoptosis induced by CO exposure. The Bcl-2 expression was significantly upregulated and Bax expression was significantly downregulated. The activity of caspase-3 and the cleaved-poly ADP-ribose polymerase expression were decreased. Taken together, our data suggest that OEC attenuates brain damages induced by acute CO poisoning within 2 weeks after transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Raub JA, Mathieu-Nolf M, Hampson NB, Thom SR (2000) Carbon monoxide poisoning—a public health perspective. Toxicology 145:1–14

    Article  CAS  PubMed  Google Scholar 

  2. Prockop LD, Chichkova RI (2007) Carbon monoxide intoxication: an updated review. J Neurol Sci 262:122–130

    Article  CAS  PubMed  Google Scholar 

  3. Lapresle J, Fardeau M (1967) The central nervous system and carbon monoxide poisoning. II. Anatomical study of brain lesions following intoxication with carbon monixide (22 cases). Prog Brain Res 24:31–74

    Article  CAS  PubMed  Google Scholar 

  4. Weaver LK (2009) Clinical practice. Carbon monoxide poisoning. N Engl J Med 360:1217–1225

    Article  CAS  PubMed  Google Scholar 

  5. Hopkins RO, Weaver LK, Valentine KJ, Mower C, Churchill S, Carlquist J (2007) Apolipoprotein E genotype and response of carbon monoxide poisoning to hyperbaric oxygen treatment. Am J Respir Crit Care Med 176:1001–1006

    Article  PubMed  Google Scholar 

  6. Weaver LK, Valentine KJ, Hopkins RO (2007) Carbon monoxide poisoning: risk factors for cognitive sequelae and the role of hyperbaric oxygen. Am J Respir Crit Care Med 176:491–497

    Article  CAS  PubMed  Google Scholar 

  7. Weaver LK, Hopkins RO, Chan KJ, Churchill S, Elliott CG, Clemmer TP, Orme JF Jr, Thomas FO, Morris AH (2002) Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 347:1057–1067

    Article  CAS  PubMed  Google Scholar 

  8. Ramon-Cueto A, Avila J (1998) Olfactory ensheathing glia: properties and function. Brain Res Bull 46:175–187

    Article  CAS  PubMed  Google Scholar 

  9. Gudino-Cabrera G, Nieto-Sampedro M (2000) Schwann-like macroglia in adult rat brain. Glia 30:49–63

    Article  CAS  PubMed  Google Scholar 

  10. Wewetzer K, Verdu E, Angelov DN, Navarro X (2002) Olfactory ensheathing glia and Schwann cells: two of a kind? Cell Tissue Res 309:337–345

    Article  PubMed  Google Scholar 

  11. Guerout N, Duclos C, Drouot L, Abramovici O, Bon-Mardion N, Lacoume Y, Jean L, Boyer O, Marie JP (2011) Transplantation of olfactory ensheathing cells promotes axonal regeneration and functional recovery of peripheral nerve lesion in rats. Muscle Nerve 43:543–551

    Article  CAS  PubMed  Google Scholar 

  12. Raisman G (2001) Olfactory ensheathing cells—another miracle cure for spinal cord injury? Nat Rev Neurosci 2:369–375

    Article  CAS  PubMed  Google Scholar 

  13. Radtke C, Aizer AA, Agulian SK, Lankford KL, Vogt PM, Kocsis JD (2009) Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair. Brain Res 1254:10–17

    Article  CAS  PubMed  Google Scholar 

  14. Ramon-Cueto A, Nieto-Sampedro M (1994) Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol 127:232–244

    Article  CAS  PubMed  Google Scholar 

  15. Li Y, Field PM, Raisman G (1997) Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277:2000–2002

    Article  CAS  PubMed  Google Scholar 

  16. Raisman G, Li Y (2007) Repair of neural pathways by olfactory ensheathing cells. Nat Rev Neurosci 8:312–319

    Article  CAS  PubMed  Google Scholar 

  17. Luo Y, Zou Y, Yang L, Liu J, Liu S, Zhou X, Zhang W, Wang T (2013) Transplantation of NSCs with OECs alleviates neuropathic pain associated with NGF downregulation in rats following spinal cord injury. Neurosci Lett 549:103–108

    Article  CAS  PubMed  Google Scholar 

  18. Shi X, Kang Y, Hu Q, Chen C, Yang L, Wang K, Chen L, Huang H, Zhou C (2010) A long-term observation of olfactory ensheathing cells transplantation to repair white matter and functional recovery in a focal ischemia model in rat. Brain Res 1317:257–267

    Article  CAS  PubMed  Google Scholar 

  19. Chen L, Xi H, Huang H, Zhang F, Liu Y, Chen D, Xiao J (2013) Multiple cell transplantation based on an intraparenchymal approach for patients with chronic phase stroke. Cell Transpl 22(Suppl 1):S83–S91

    Article  Google Scholar 

  20. Bliss T, Guzman R, Daadi M, Steinberg GK (2007) Cell transplantation therapy for stroke. Stroke 38:817–826

    Article  PubMed  Google Scholar 

  21. Chiu SC, Hung HS, Lin SZ, Chiang E, Liu DD (2009) Therapeutic potential of olfactory ensheathing cells in neurodegenerative diseases. J Mol Med (Berl) 87:1179–1189

    Article  Google Scholar 

  22. Shyu WC, Liu DD, Lin SZ, Li WW, Su CY, Chang YC, Wang HJ, Wang HW, Tsai CH, Li H (2008) Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke. J Clin Investig 118:2482–2495

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Thom SR, Bhopale VM, Fisher D, Zhang J, Gimotty P (2004) Delayed neuropathology after carbon monoxide poisoning is immune-mediated. Proc Natl Acad Sci USA 101:13660–13665

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Agrawal AK, Shukla S, Chaturvedi RK, Seth K, Srivastava N, Ahmad A, Seth PK (2004) Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson’s disease: a cotransplantation approach with fetal ventral mesencephalic cells. Neurobiol Dis 16:516–526

    Article  CAS  PubMed  Google Scholar 

  25. Srivastava N, Seth K, Khanna VK, Ansari RW, Agrawal AK (2009) Long-term functional restoration by neural progenitor cell transplantation in rat model of cognitive dysfunction: co-transplantation with olfactory ensheathing cells for neurotrophic factor support. Int J Dev Neurosci 27:103–110

    Article  CAS  PubMed  Google Scholar 

  26. Lankford KL, Brown RJ, Sasaki M, Kocsis JD (2014) Olfactory ensheathing cells, but not Schwann cells, proliferate and migrate extensively within moderately X-irradiated juvenile rat brain. Glia 62:52–63

    Article  PubMed  Google Scholar 

  27. Chuah MI, Choi-Lundberg D, Weston S, Vincent AJ, Chung RS, Vickers JC, West AK (2004) Olfactory ensheathing cells promote collateral axonal branching in the injured adult rat spinal cord. Exp Neurol 185:15–25

    Article  CAS  PubMed  Google Scholar 

  28. Tharion G, Indirani K, Durai M, Meenakshi M, Devasahayam SR, Prabhav NR, Solomons C, Bhattacharji S (2011) Motor recovery following olfactory ensheathing cell transplantation in rats with spinal cord injury. Neurol India 59:566–572

    Article  PubMed  Google Scholar 

  29. Ferrero-Gutierrez A, Menendez-Menendez Y, Alvarez-Viejo M, Meana A, Otero J (2013) New serum-derived albumin scaffold seeded with adipose-derived stem cells and olfactory ensheathing cells used to treat spinal cord injured rats. Histol Histopathol 28:89–100

    CAS  PubMed  Google Scholar 

  30. Torres-Espin A, Redondo-Castro E, Hernandez J, Navarro X (2014) Bone marrow mesenchymal stromal cells and olfactory ensheathing cells transplantation after spinal cord injury—a morphological and functional comparison in rats. Eur J Neurosci 39:1704–1717

  31. Rao Y, Zhu W, Liu H, Jia C, Zhao Q, Wang Y (2013) Clinical application of olfactory ensheathing cells in the treatment of spinal cord injury. J Int Med Res 41:473–481

    Article  CAS  PubMed  Google Scholar 

  32. Huang H, Chen L, Xi H, Wang H, Zhang J, Zhang F, Liu Y (2008) Fetal olfactory ensheathing cells transplantation in amyotrophic lateral sclerosis patients: a controlled pilot study. Clin Transpl 22:710–718

    Article  Google Scholar 

  33. Morita E, Watanabe Y, Ishimoto M, Nakano T, Kitayama M, Yasui K, Fukada Y, Doi K, Karunaratne A, Murrell WG, Sutharsan R, Mackay-Sim A, Hata Y, Nakashima K (2008) A novel cell transplantation protocol and its application to an ALS mouse model. Exp Neurol 213:431–438

    Article  CAS  PubMed  Google Scholar 

  34. Wang W, Tian L, Li Y, Wang X, Xia F, Li L, Li J, Zhang Z (2013) Effects of hydrogen-rich saline on rats with acute carbon monoxide poisoning. J Emerg Med 44:107–115

    Article  PubMed  Google Scholar 

  35. Sun X, Xu H, Meng X, Qi J, Cui Y, Li Y, Zhang H, Xu L (2013) Potential use of hyperoxygenated solution as a treatment strategy for carbon monoxide poisoning. PLoS ONE 8:e81779

    Article  PubMed Central  PubMed  Google Scholar 

  36. Wang YC, Xia QJ, Ba YC, Wang TY, Lin N, Zou Y, Shang FF, Zhou XF, Wang TH, Fu XM, Qi JG (2014) Transplantation of olfactory ensheathing cells promotes the recovery of neurological functions in rats with traumatic brain injury associated with downregulation of Bad. Cytotherapy 16:1000–1010

  37. Wu A, Lauschke JL, Gorrie CA, Cameron N, Hayward I, Mackay-Sim A, Waite PM (2011) Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury. Exp Neurol 229:143–157

    Article  PubMed  Google Scholar 

  38. Bogen IL, Jensen V, Hvalby O, Walaas SI (2011) Glutamatergic neurotransmission in the synapsin I and II double knock-out mouse. Semin Cell Dev Biol 22:400–407

    Article  CAS  PubMed  Google Scholar 

  39. Lopez IA, Acuna D, Beltran-Parrazal L, Lopez IE, Amarnani A, Cortes M, Edmond J (2009) Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air). BMC Neurosci 10:53

    Article  PubMed Central  PubMed  Google Scholar 

  40. Kruger L, Bendotti C, Rivolta R, Samanin R (1993) Distribution of GAP-43 mRNA in the adult rat brain. J Comp Neurol 333:417–434

    Article  CAS  PubMed  Google Scholar 

  41. Carulli D, Buffo A, Strata P (2004) Reparative mechanisms in the cerebellar cortex. Prog Neurobiol 72:373–398

    Article  CAS  PubMed  Google Scholar 

  42. Ramon-Cueto A (2000) Olfactory ensheathing glia transplantation into the injured spinal cord. Prog Brain Res 128:265–272

    Article  CAS  PubMed  Google Scholar 

  43. Rao Y, Zhu W, Guo Y, Jia C, Qi R, Qiao R, Cao D, Zhang H, Cui Z, Yang L, Wang Y (2013) Long-term outcome of olfactory ensheathing cell transplantation in six patients with chronic complete spinal cord injury. Cell Transpl 22(Suppl 1):S21–S25

    Article  Google Scholar 

  44. Piantadosi CA, Tatro L, Zhang J (1995) Hydroxyl radical production in the brain after CO hypoxia in rats. Free Radical Biol Med 18:603–609

    Article  CAS  Google Scholar 

  45. Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D (2002) Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 54:271–284

    Article  CAS  PubMed  Google Scholar 

  46. Yavuz Y, Mollaoglu H, Yurumez Y, Ucok K, Duran L, Tunay K, Akgun L (2013) Therapeutic effect of magnesium sulphate on carbon monoxide toxicity-mediated brain lipid peroxidation. Eur Rev Med Pharmacol Sci 17(Suppl 1):28–33

    PubMed  Google Scholar 

  47. Adams JM (2003) Ways of dying: multiple pathways to apoptosis. Genes Dev 17:2481–2495

    Article  CAS  PubMed  Google Scholar 

  48. Shi Y (2006) Mechanical aspects of apoptosome assembly. Curr Opin Cell Biol 18:677–684

    Article  CAS  PubMed  Google Scholar 

  49. Bratton SB, MacFarlane M, Cain K, Cohen GM (2000) Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Exp Cell Res 256:27–33

    Article  CAS  PubMed  Google Scholar 

  50. Adams JM, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26:1324–1337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Emergency Medicine, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People’s Republic of China

    Wei Liu, Qiang Zheng, Yu Wang, Xinfei Han, Li Yuan & Min Zhao

Authors
  1. Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiang Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinfei Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Min Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Min Zhao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, W., Zheng, Q., Wang, Y. et al. Transplantation of Olfactory Ensheathing Cells Attenuates Acute Carbon Monoxide Poisoning-Induced Brain Damages in Rats. Neurochem Res 40, 70–80 (2015). https://doi.org/10.1007/s11064-014-1467-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-014-1467-z

Keywords

Search

Navigation