J.Z. Yu

Fasudil Enhances Therapeutic Efficacy of Neural Stem Cells in the Mouse Model of MPTP-Induced Parkinson’s Disease

Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model and explored the possible cellular and molecular mechanisms. The results clearly show that combined treatment of NSCs with fasudil further improves motor capacity of PD mice, thus exerting double effect in treating MPTP-PD. The combined intervention more effectively protected dopaminergic (DA) neurons from loss in the substantia nigra pars compacta (SNpc), which may be associated with the increased number and survival of transplanted NSCs in the brain. Compared with the treatment of fasudil or NSCs alone, the combined intervention more effectively inhibited the activation and aggregation of microglia and astrocytes, displayed stronger anti-inflammatory and antioxidant effects, induced more neurotrophic factor NT-3, and affected the dynamic homeostasis of NMDA and AMPA receptors in MPTP-PD mice. Our study demonstrates that intranasal administration of NSCs, followed by fasudil administration, is a promising cell-based therapy for neuronal lesions.

Synergistic and Superimposed Effect of Bone Marrow-Derived Mesenchymal Stem Cells Combined with Fasudil in Experimental Autoimmune Encephalomyelitis

Bone marrow-derived mesenchymal stem cells (MSCs) are the ideal transplanted cells of cellular therapy for promoting neuroprotection and neurorestoration. However, the optimization of transplanted cells and the improvement of microenvironment around implanted cells are still two critical challenges for enhancing therapeutic effect. In the current study, we observed the therapeutic potential of MSCs combined with Fasudil in mouse model of experimental autoimmune encephalomyelitis (EAE) and explored possible mechanisms of action. The results clearly show that combined intervention of MSCs and Fasudil further reduced the severity of EAE compared with MSCs or Fasudil alone, indicating a synergistic and superimposed effect in treating EAE. The addition of Fasudil inhibited MSC-induced inflammatory signaling TLR-4/MyD88 and inflammatory molecule IFN-γ, IL-1β, and TNF-α but did not convert M1 microglia to M2 phenotype. The delivery of MSCs enhanced the expression of glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) compared with that of Fasudil. Importantly, combined intervention of MSCs and Fasudil further increased the expression of BDNF and GDNF compared with the delivery of MSCs alone, indicating that combined intervention of MSCs and Fasudil synergistically contributes to the expression of neurotrophic factors which should be related to the expression of increased galactocerebroside (GalC) compared with mice treated with Fasudil and MSCs alone. However, a lot of investigation is warranted to further elucidate the cross talk of MSCs and Fasudil in the therapeutic potential of EAE/multiple sclerosis.

Safflower yellow inhibits the inflammatory response and regulates microglial polarization in LPS-stimulated bv2 cells

myositis (2) indirect effects due to metabolic complications resulting in encephalopathy and cerebrovascular complications due to thrombocytopenia and platelet dysfunction and (3) postinfectious immunemediated acute disseminated encephalomyelitis, Guillain Barre syndrome and optic neuritis. Material and methods: This was a descriptive cross sectional study including seropositive patients diagnosed with Dengue fever (DF), Dengue with warning signs and Severe Dengue with neurological manifestations presenting to Medicine Department of LLR Hospital, Kanpur. Results: 10 (2.6%) patients had neurological manifestations out of 383 seropositive patients. Out of ten, nine patients were male and only one patient was female. Among them 10% patients come under category of classical dengue fever, 10% patients suffered from dengue with warning signs and 80% with severe dengue .4 patients had encephalopathy,3 other patients had encephalitis, 2 patients presented with single episode of symptomatic generalized seizure and 1 patient presented as having an intra cranial hemorrhage. Conclusions: Neurological manifestations of dengue are manifold and it is necessary to consider dengue as a cause for the above neurological presentations in endemic zones of the disease.