Neuroprotective Effects of Brain-Derived Neurotrophic Factor and Noggin-Modified Bone Mesenchymal Stem Cells in Focal Cerebral Ischemia in Rats

Autor: Li Sun, Nan Zhang, Hongyan Lu, Xiaodong Zhu, Hao Liang, Xingmiao Liu, Yan Cheng
Rok vydání: 2015
Předmět:
0301 basic medicine
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Mesenchymal Stem Cell Transplantation
Neuroprotection
Brain Ischemia
Brain ischemia
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
stomatognathic system
Neurotrophic factors
Internal medicine
medicine
Animals
Noggin
bcl-2-Associated X Protein
Brain-derived neurotrophic factor
business.industry
Brain-Derived Neurotrophic Factor
Rehabilitation
Brain
hemic and immune systems
Mesenchymal Stem Cells
medicine.disease
Rats
Transplantation
Vascular endothelial growth factor
Vascular endothelial growth factor A
030104 developmental biology
Endocrinology
Neuroprotective Agents
Treatment Outcome
chemistry
Matrix Metalloproteinase 9
Immunology
Surgery
Neurology (clinical)
Cardiology and Cardiovascular Medicine
business
Carrier Proteins
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Zdroj: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 25(2)
ISSN: 1532-8511
Popis: Background Administration of bone marrow stromal cells (BMSCs) has been reported to ameliorate functional deficits in rat ischemia models. In the present study, we tried to reveal the underlying mechanism of the improvement of neurological function after stroke by BMSCs transfected with brain-derived neurotrophic factor (BDNF) and/or Noggin . Methods BMSCs were transfected with BDNF or/and Noggin using the adenovirus method. Middle cerebral artery occlusion (MCAO) rat models were treated with different types of transfected BMSCs. The treatment effect was assessed by measuring the modified Neurological Severity Score and the expression levels of different stroke-related molecules using Western blot, immunohistochemistry assay (IHC), and enzyme-linked immunosorbent assay (ELISA). Results The injection of BDNF or/and Noggin -modified BMSCs could significantly improve the neurological function of MCAO animals. Western blot and IHC staining showed that the expression levels of vascular endothelial growth factor, BCL-2, p-GSK3β, and p-Akt were significantly upregulated, while the expressions of Bax, TLR4, and MyD88 were significantly downregulated. Moreover, ELISA assay revealed that the level of matrix metallopeptidase 9 (MMP-9) and reactive oxygen species were also significantly decreased. These results suggested that the treatment of BDNF or/and Noggin -modified BMSCs may suppress the ischemia-induced apoptosis and inflammation in the model animals, which might be through the Akt/GSK3β and TLR4/MyD88 pathways. Conclusion BDNF or/and Noggin -modified BMSCs may exert neuroprotective effects through the Akt/GSK3β and TLR4/MyD88 pathways. Transplantation of BDNF or/and Noggin -modified BMSCs might be a potential therapeutic method for ischemic stroke in clinics.
Databáze: OpenAIRE
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