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Neurosurgery. 2011 Mar;68(3):691-704. doi: 10.1227/NEU.0b013e3182098a8a.

Neuroprotective effects of bone marrow stem cells overexpressing glial cell line-derived neurotrophic factor on rats with intracerebral hemorrhage and neurons exposed to hypoxia/reoxygenation.

Author information

1
Department of Anatomy and Neurobiology, Tongji University School of Medicine, and Department of Plastic and Reconstructive Surgery, 9th People's Hospital, Shanghai, China.

Abstract

BACKGROUND:

Intracerebral hemorrhage (ICH) represents at least 15% of all strokes in the Western population and a considerably higher proportion at 50% to 60% in the Oriental population.

OBJECTIVE:

To investigate whether administration of bone marrow stem cells (BMSCs) overexpressing glial cell line-derived neurotrophic factor (GDNF) provides more efficient neuroprotection for rats with ICH and neurons exposed to hypoxia/reoxygenation.

METHODS:

Primary rat BMSCs were transfected with rat GDNF gene using virus vector (GDNF/BMSCs) and blank virus plasmid (BVP/BMSCs). Primary rat cortical neurons of rats were exposed to hypoxia and then reoxygenated with GDNF/BMSCs (GDNF/BMSCs group) or BVP/BMSCs (BMSCs group) treatment for 12 hours and 1, 2, 3, and 5 days. Hoechst 33258 staining was used to evaluate apoptosis. GDNF/BMSCs, BVP/BMSCs, and saline (GDNF/BMSCs, BMSCs, and control groups) were injected into the right striatum 3 days after rat ICH induced by injecting collagenase. Modified neurological severity scores and hematoxylin and eosin staining were performed to evaluate neurological function and lesion volume at 1 and 2 weeks after transplantation. Immunostaining was used to observe differentiation of grafted cells (neurofilament-200 for neurons, glial fibrillary acidic protein for astrocytes). The GDNF level and apoptosis were evaluated by Western blotting and terminal deoxynucleotidyl transferase dUTP nick-end labeling, respectively.

RESULTS:

The GDNF/BMSCs group had significantly lowered apoptosis compared with the BMSCs group at the given time. The GDNF/BMSCs group had significantly improved functional deficits and reduced lesion volume compared with the BMSCs group. Stable GDNF expression in the GDNF/BMSCs group was detected at the given time in the host brain. The neurofilament-positive grafted cells in the GDNF/BMSCs group were more numerous than in the BMSCs group. The GDNF/BMSCs group had significantly decreased apoptotic cells compared with the BMSCs group.

CONCLUSION:

These results suggest that GDNF/BMSCs provide better neuroprotection for rats with ICH and neurons exposed to hypoxia/reoxygenation.

PMID:
21311297
DOI:
10.1227/NEU.0b013e3182098a8a
[Indexed for MEDLINE]

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