Advertisement

Topical Therapy with Mesenchymal Stem Cells Following an Acute Experimental Head Injury Has Benefits in Motor-Behavioral Tests for Rodents

Chapter
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 122)

Abstract

Background: The neuroprotective effects of mesenchymal stem cells (MSCs) have been reported in rodent and in preliminary clinical studies. MSCs are usually transplanted to patients by systemic infusion. However, only a few of the infused MSCs are delivered to the brain because of pulmonary trapping and the blood–brain barrier. In this study, MSCs were topically applied to the site of traumatic brain injury (TBI) and the neuroprotective effects were assessed. Materials and Methods: TBI was induced in Sprague–Dawley (SD) rats with an electromagnetically controlled cortical impact device after craniotomy was performed between the bregma and lambda, 1 mm lateral to the midline. We applied 1.5 million MSCs, derived from the adipose tissue of transgenic green fluorescent protein (GFP)-SD rats, to the exposed cerebral cortex at the injured site. The MSCs were held in position by a thin layer of fibrin. Neurological function in the test (n = 10) and control (n = 10) animals was evaluated using the rotarod test, the water maze test, and gait analysis at different time points. Results: Within 5 days following topical application, GFP-positive cells were found in the brain parenchyma. These cells co-expressed with markers of Glial fibrillary acidic protein (GFAP), nestin, and NeuN. There was less neuronal death in CA1 and CA3 of the hippocampus in the test animals. Neurological functional recovery was significantly improved. Conclusion: Topically applied MSCs can migrate to the injured brain parenchyma and offer neuroprotective effects.

Keywords

Mesenchymal stem cells Topical application Traumatic brain injury 
This is a preview of subscription content, log in to check access.

Notes

Conflict of Interest

No conflict of interest exists for any of the authors.

References

  1. 1.
    Sande A, West C (2010) Traumatic brain injury: a review of pathophysiology and management. J Vet Emerg Crit Care 20:177–190CrossRefGoogle Scholar
  2. 2.
    Bagiella E, Novack TA, Ansel B, Diaz-Arrastia R, Dikmen S, Temkin HN (2010) Measuring outcome in traumatic brain injury treatment trials: recommendations from traumatic brain injury trials network. J Head Trauma Rehabil 25:375–382CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD (1999) Multilineage potential of adult mesenchymal stem cells. Science 284:143–147CrossRefPubMedGoogle Scholar
  4. 4.
    Mahmood A, Lu D, Lu M, Chopp M (2003) Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells. Neurosurgery 53:697–702CrossRefPubMedGoogle Scholar
  5. 5.
    Li Y, Chopp M (2009) Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci Lett 456:120–123CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Joyce N, Annett G, Wirthin L, Olson S, Bauer G, Nolta JA (2010) Mesenchymal stem cells for treatment of neurodegenerative disease. Regen Med 5:933–946CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Yoon JK, Park BN, Shim WY, Shin JY, Lee G, Ahn YH (2010) In vivo tracking of 111In-labeled bone marrow mesenchymal stem cells in acute brain trauma model. Nucl Med Biol 37:381–388CrossRefPubMedGoogle Scholar
  8. 8.
    Lam PK, Lo AWI, Wang KKW, Lau HCH, Leung KKC, Li KTC, Lai PBS, Poon WS (2013) Transplantation of mesenchymal stem cells to the brain by topical application in an experimental traumatic injury. J Clin Neurosci 20:306–309CrossRefPubMedGoogle Scholar
  9. 9.
    Brody DL, Donald CM, Kessens CC, Yeude C, Parsadanian M, Spinner M, Kim E, Schwetye KE, Holtzman DM, Bayly PV (2007) Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury. J Neurotrauma 24:657–673CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Brandeis R, Brandys Y, Yehuda S (1989) The use of Morris Water Maze in the study of memory and learning. Int J Neurosci 48:29–69CrossRefPubMedGoogle Scholar
  11. 11.
    Ray SK, Dixon CE, Banik NL (2002) Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol 17:1137–1152PubMedGoogle Scholar
  12. 12.
    Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596PubMedPubMedCentralGoogle Scholar
  13. 13.
    Walker PA, Shah SK, Harting MT, Cox CS (2009) Progenitor cell therapy for traumatic brain injury: barriers and opportunities in translation. Dis Model Mech 2:23–38CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chopp M, Mahmood A, Lu D, Li Y (2009) Mesenchymal stem cell treatment of traumatic brain injury. J Neurosurg 110:1186–1188CrossRefPubMedGoogle Scholar
  15. 15.
    Lam PK, Ng CF, To KF, Ng SSM, Mak TWC, Lo AWI, Lai FMM, Poon WS, Lai PBS (2011) Topical application of mesenchymal stem cells to somatic organs—a preliminary report. Transplantation 19:e9–e11CrossRefGoogle Scholar
  16. 16.
    Rose SE, Leipold C, Terregino C, O’Malley KF (1998) Efficacy of the motor component of the Glasgow Coma Scale in trauma triage. J Trauma 45:42–44CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Division of Neurosurgery, Department of SurgeryThe Chinese University of Hong Kong, Prince of Wales HospitalShatin, Hong KongChina
  2. 2.Department of Anatomical and Cellular PathologyThe Chinese University of Hong Kong, Prince of Wales HospitalShatin, Hong KongChina
  3. 3.Department of Psychiatry and NeuroscienceCenter of Neuroproteomics and Biomarkers Research, University of FloridaGainesvilleUSA
  4. 4.Chow Tai Fook-Cheng Yu Tung Surgical Stem cell Research CenterThe Chinese University of Hong Kong, Prince of Wales HospitalShatin, Hong KongChina

Personalised recommendations

Cite chapter

Buy options