Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
권호 표지
DOI QR코드

DOI QR Code

In Vivo Spinal Distribution of Cy5.5 Fluorescent Dye after Injection via the Lateral Ventricle and Cisterna Magna in Rat Model

  • Lee, Kee-Hang (Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University) ;
  • Nam, Hyun (Single Cell Network Research Center, Sungkyunkwan University School of Medicine) ;
  • Won, Jeong-Seob (Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University) ;
  • Hwang, Ji-Yoon (Single Cell Network Research Center, Sungkyunkwan University School of Medicine) ;
  • Jang, Hye Won (Department of Medical Education, Sungkyunkwan University School of Medicine) ;
  • Lee, Sun-Ho (Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University) ;
  • Joo, Kyeung Min (Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University)
  • Received : 2017.09.18
  • Accepted : 2017.10.23
  • Published : 2018.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Objective : The purpose of this study was to find an optimal delivery route for clinical trials of intrathecal cell therapy for spinal cord injury in preclinical stage. Methods : We compared in vivo distribution of Cy5.5 fluorescent dye in the spinal cord region at various time points utilizing in vivo optical imaging techniques, which was injected into the lateral ventricle (LV) or cisterna magna (CM) of rats. Results : Although CM locates nearer to the spinal cord than the LV, significantly higher signal of Cy5.5 was detected in the thoracic and lumbar spinal cord region at all time points tested when Cy5.5 was injected into the LV. In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was observed within 12 hours after injection, which was maintained until 72 hours after injection. In contrast, Cy5.5 signal was concentrated at the injection site in the CM injection at all time points. Conclusion : These data suggested that the LV might be suitable for preclinical injection route of therapeutics targeting the spinal cord to test their treatment efficacy and biosafety for spinal cord diseases in small animal models.

Keywords

References

  1. Bjorklund A, Lindvall O : Cell replacement therapies for central nervous system disorders. Nat Neurosci 3 : 537-544, 2000 https://doi.org/10.1038/75705
  2. Boulton M, Flessner M, Armstrong D, Mohamed R, Hay J, Johnston M : Contribution of extracranial lymphatics and arachnoid villi to the clear- ance of a CSF tracer in the rat. Am J Physiol 276 : R818-R823, 1999
  3. Bradbury MW, Lathem W : A flow of cerebrospinal fluid along the cen- tral canal of the spinal cord of the rabbit and communications between this canal and the sacral subarachnoid space. J Physiol 181 : 785-800, 1965 https://doi.org/10.1113/jphysiol.1965.sp007797
  4. Chen Y, Imai H, Ito A, Saito N : Novel modified method for injection into the cerebrospinal fluid via the cerebellomedullary cistern in mice. Acta Neurobiol Exp (Wars) 73 : 304-311, 2013
  5. Consiglio AR, Lucion AB : Technique for collecting cerebrospinal fluid in the cisterna magna of non-anesthetized rats. Brain Res Brain Res Protoc 5 : 109-114, 2000 https://doi.org/10.1016/S1385-299X(99)00062-8
  6. Feldman EL, Boulis NM, Hur J, Johe K, Rutkove SB, Federici T, et al. : Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes. Ann Neurol 75 : 363-373, 2014 https://doi.org/10.1002/ana.24113
  7. Gao GH, Park MJ, Li Y, Im GH, Kim JH, Kim HN, et al. : The use of pH-sensitive positively charged polymeric micelles for protein delivery. Biomaterials 33 : 9157-9164, 2012 https://doi.org/10.1016/j.biomaterials.2012.09.016
  8. Johnston M, Zakharov A, Koh L, Armstrong D : Subarachnoid injection of Microfil reveals connections between cerebrospinal fluid and nasal lymphatics in the non-human primate. Neuropathol Appl Neurobiol 31 : 632-640, 2005 https://doi.org/10.1111/j.1365-2990.2005.00679.x
  9. Kim SU, de Vellis J : Stem cell-based cell therapy in neurological diseases: a review. J Neurosci Res 87 : 2183-2200, 2009 https://doi.org/10.1002/jnr.22054
  10. Koedel U, Bernatowicz A, Frei K, Fontana A, Pfister HW : Systemically (but not intrathecally) administered IL-10 attenuates pathophysiologic alterations in experimental pneumococcal meningitis. J Immunol 157 : 5185-5191, 1996
  11. Lindvall O, Kokaia Z, Martinez-Serrano A : Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med 10 Suppl : S42-S50, 2004 https://doi.org/10.1038/nm1064
  12. Liu L, Duff K : A technique for serial collection of cerebrospinal fluid from the cisterna magna in mouse. J Vis Exp (21) : 960, 2008
  13. Proescholdt MG, Hutto B, Brady LS, Herkenham M : Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [14C]inulin in rat. Neuroscience 95 : 577-592, 2000
  14. Rowland JW, Hawryluk GW, Kwon B, Fehlings MG : Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus 25 : E2, 2008
  15. Shirao S, Fujisawa H, Kudo A, Kurokawa T, Yoneda H, Kunitsugu I, et al. : Inhibitory effects of eicosapentaenoic acid on chronic cerebral vasospasm after subarachnoid hemorrhage: possible involvement of a sphingosylphosphorylcholine-rho-kinase pathway. Cerebrovasc Dis 26 : 30-37, 2008
  16. van der Flier M, Coenjaerts FE, Mwinzi PN, Rijkers E, Ruyken M, Scharringa J, et al. : Antibody neutralization of vascular endothelial growth factor (VEGF) fails to attenuate vascular permeability and brain edema in experimental pneumococcal meningitis. J Neuroimmunol 160 : 170-177, 2005 https://doi.org/10.1016/j.jneuroim.2004.11.013
  17. Yang HY, Jang MS, Li Y, Lee JH, Lee DS : Multifunctional and redox-responsive self-assembled magnetic nanovectors for protein delivery and dual-modal imaging. ACS Appl Mater Interfaces 9 : 19184-19192, 2017 https://doi.org/10.1021/acsami.7b03747

Cited by

  1. In vivo distribution of U87MG cells injected into the lateral ventricle of rats with spinal cord injury vol.13, pp.8, 2018, https://doi.org/10.1371/journal.pone.0202307