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Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
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.
- Subjects :
- Cell Survival
Pharmacology
blood–brain barrier
Blood–brain barrier
Hippocampus
Umbilical cord
Rats, Sprague-Dawley
stem cells
Neurotrophic factors
medicine
Glial cell line-derived neurotrophic factor
Animals
Humans
Mannitol
Nerve Growth Factors
neurotrophic factor
cerebral palsy
Behavior, Animal
biology
business.industry
Graft Survival
Brain
Articles
Dendrites
Cell Biology
Rats
Up-Regulation
Transplantation
medicine.anatomical_structure
Nerve growth factor
Animals, Newborn
Anesthesia
Hypoxia-Ischemia, Brain
biology.protein
Molecular Medicine
Cord Blood Stem Cell Transplantation
Stem cell
business
transplantation
medicine.drug
Subjects
Details
- ISSN :
- 15821838
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....e66aca64baadc5114bb305fe292661b3