Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease
| Autor: | Yin Xia Chao, Samuel Sam Wah Tay, Bei Ping He |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Dopamine Immunology Substantia nigra Pharmacology Biology Mesenchymal Stem Cell Transplantation Blood–brain barrier Mice chemistry.chemical_compound Parkinsonian Disorders medicine Animals Immunology and Allergy Gliosis Infusions Intravenous Cells Cultured Neuroinflammation Neurons Cell Death Microglia Pars compacta MPTP Dopaminergic Membrane Proteins nervous system diseases Mice Inbred C57BL Substantia Nigra Transplantation Disease Models Animal Mannose-Binding Lectins Treatment Outcome medicine.anatomical_structure Liver nervous system Neurology chemistry Blood-Brain Barrier Nerve Degeneration cardiovascular system Encephalitis Neurology (clinical) |
| Zdroj: | Journal of Neuroimmunology. 216:39-50 |
| ISSN: | 0165-5728 |
| Popis: | Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons. |
| Databáze: | OpenAIRE |
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