Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts

Takao Yasuhara, K. Hara, M. Maki, L. Xu, G. Yu, M. M. Ali, T. Masuda, S. J. Yu, E. K. Bae, T. Hayashi, N. Matsukawa, Y. Kaneko, N. Kuzmin-Nichols, S. Ellovitch, E. L. Cruz, S. K. Klasko, C. D. Sanberg, P. R. Sanberg, C. V. Borlongan

Research output: Contribution to journalArticle

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Abstract

We recently demonstrated that blood-brain barrier permeabilization using mannitol enhances the therapeutic efficacy of systemically administered human umbilical cord blood (HUCB) by facilitating the entry of neurotrophic factors from the periphery into the adult stroke brain. Here, we examined whether the same blood-brain barrier manipulation approach increases the therapeutic effects of intravenously delivered HUCB in a neonatal hypoxic-ischaemic (HI) injury model. Seven-day-old Sprague-Dawley rats were subjected to unilateral HI injury and then at day 7 after the insult, animals intravenously received vehicle alone, mannitol alone, HUCB cells (15k mononuclear fraction) alone or a combination of mannitol and HUCB cells. Behavioural tests at post-transplantation days 7 and 14 showed that HI animals that received HUCB cells alone or when combined with mannitol were significantly less impaired in motor asymmetry and motor coordination compared with those that received vehicle alone or mannitol alone. Brain tissues from a separate animal cohort from the four treatment conditions were processed for enzyme-linked immunosorbent assay at day 3 post-transplantation, and revealed elevated levels of GDNF, NGF and BDNF in those that received HUCB cells alone or when combined with mannitol compared with those that received vehicle or mannitol alone, with the combined HUCB cells and mannitol exhibiting the most robust neurotropic factor up-regulation. Histological assays revealed only sporadic detection of HUCB cells, suggesting that the trophic factor-mediated mechanism, rather than cell replacement per se, principally contributed to the behavioural improvement. These findings extend the utility of blood-brain barrier permeabilization in facilitating cell therapy for treating neonatal HI injury.

Original languageEnglish
Pages (from-to)914-921
Number of pages8
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

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Nerve Growth Factors
Mannitol
Fetal Blood
Up-Regulation
Transplants
Blood Cells
Blood-Brain Barrier
Wounds and Injuries
Transplantation
Glial Cell Line-Derived Neurotrophic Factor
Brain-Derived Neurotrophic Factor
Brain
Therapeutic Uses
Nerve Growth Factor
Cell- and Tissue-Based Therapy
Sprague Dawley Rats
Enzyme-Linked Immunosorbent Assay
Stroke
Therapeutics

Keywords

  • Blood-brain barrier
  • Cerebral palsy
  • Neurotrophic factor
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts. / Yasuhara, Takao; Hara, K.; Maki, M.; Xu, L.; Yu, G.; Ali, M. M.; Masuda, T.; Yu, S. J.; Bae, E. K.; Hayashi, T.; Matsukawa, N.; Kaneko, Y.; Kuzmin-Nichols, N.; Ellovitch, S.; Cruz, E. L.; Klasko, S. K.; Sanberg, C. D.; Sanberg, P. R.; Borlongan, C. V.

In: Journal of Cellular and Molecular Medicine, Vol. 14, No. 4, 04.2010, p. 914-921.

Research output: Contribution to journalArticle

Yasuhara, T, Hara, K, Maki, M, Xu, L, Yu, G, Ali, MM, Masuda, T, Yu, SJ, Bae, EK, Hayashi, T, Matsukawa, N, Kaneko, Y, Kuzmin-Nichols, N, Ellovitch, S, Cruz, EL, Klasko, SK, Sanberg, CD, Sanberg, PR & Borlongan, CV 2010, 'Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts', Journal of Cellular and Molecular Medicine, vol. 14, no. 4, pp. 914-921. https://doi.org/10.1111/j.1582-4934.2008.00671.x
Yasuhara, Takao ; Hara, K. ; Maki, M. ; Xu, L. ; Yu, G. ; Ali, M. M. ; Masuda, T. ; Yu, S. J. ; Bae, E. K. ; Hayashi, T. ; Matsukawa, N. ; Kaneko, Y. ; Kuzmin-Nichols, N. ; Ellovitch, S. ; Cruz, E. L. ; Klasko, S. K. ; Sanberg, C. D. ; Sanberg, P. R. ; Borlongan, C. V. / Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts. In: Journal of Cellular and Molecular Medicine. 2010 ; Vol. 14, No. 4. pp. 914-921.
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AU - Yu, G.

AU - Ali, M. M.

AU - Masuda, T.

AU - Yu, S. J.

AU - Bae, E. K.

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AU - Matsukawa, N.

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