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Abstract
Gradual loss of neuronal structure and function due to impaired blood–brain barrier (BBB) and neuroinflammation are important factors in multiple sclerosis (MS) progression. Our previous studies demonstrated that the C16 peptide and angiopoietin 1 (Ang-1) compound (C + A) could modulate inflammation and vascular protection in many models of MS. In this study, nanotechnology and a novel nanovector of the leukocyte chemotactic peptide N-formyl-methionyl-leucyl–phenylalanine (fMLP) were used to examine the effects of C + A on MS. The acute experimental autoimmune encephalomyelitis (EAE) model of MS was established in Lewis rats. The C + A compounds were conjugated to control nano-carriers and fMLP-nano-carriers and administered to animals by intravenous injection. The neuropathological changes in the brain cortex and spinal cord were examined using multiple approaches. The stimulation of vascular injection sites was examined using rabbits. The results showed that all C + A compounds (C + A alone, nano-carrier C + A, and fMLP-nano-carrier C + A) reduced neuronal inflammation, axonal demyelination, gliosis, neuronal apoptosis, vascular leakage, and BBB impairment induced by EAE. In addition, the C + A compounds had minimal side effects on liver and kidney functions. Furthermore, the fMLP-nano-carrier C + A compound had better effects compared to C + A alone and the nano-carrier C + A. This study indicated that the fMLP-nano-carrier C + A could attenuate inflammation-related pathological changes in EAE and may be a potential therapeutic strategy for the treatment of MS and EAE.
Acknowledgments
The authors thank Medjaden Inc. for helping in editing and proofreading the manuscript.
Author contributions
SH and WJ conceived and designed the study; XXF, HHC, QH, and HJ carried out the experiments; XXF and HHC performed data analysis and interpreted the data; SH and HYC wrote the initial draft. All authors have reviewed and approved the final manuscript.
Institutional review board statement
Experiments were carried out in accordance with NIH Guidelines for the Care and Use of Laboratory Animals, with approval from the Animal Ethics Committee at Zhejiang University (NO.25327) and have adhered to the ARRIVE guidelines. Since the animals need to be taken tissue at 2 and 4 weeks two time point, both fresh tissue used for WB and fixed tissue for histological assay were needed, and some animals might dead during experiment, 20 animals were arranged in each group. The rats were placed in a temperature- and humidity-controlled chambers. Manual bladder emptying was performed at least three times daily when the clinic score of animal reached 4. Animals were sacrificed under deep anesthesia with sodium pentobarbital (40 mg/kg i.p.). This study took 106 Lewis rats (100 for observing the effects of different drugs delivery on MS treatment and 6 for detecting of vascular wall stimulation in different groups).Six male adult health rabbits were taken also for detecting of vascular wall stimulation.
Disclosure statement
The authors declared that there was no conflict of interest.
Data availability statement
The supporting data for the results of this study can be obtained by contacting the corresponding author under reasonable request.