Neuroprotective effect of immunomodulatory peptides in rats with traumatic spinal cord injury

Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury(SCI).Nevertheless, neither strategy has achieved a convincing effect.We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI.The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor(MLIF), A91 peptide, and glutathione monoethyl ester(GSH-MEE) on chronic-stage spinal cord injury.Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion.Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE.Two months after injury, motor functional recovery was evaluated using the open field test.Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively.The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively.Collagen deposition was evaluated using Masson's trichrome staining.The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area.The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI.This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116(approval date November 30, 2015) and R-2017-3603-33(approval date June 5, 2017).

Neuroprotective effects of vascular endothelial growth factor A in the experimental autoimmune encephalomyelitis model of multiple sclerosis

Multiple sclerosis（MS）is a chronic inflammatory disease of the central nervous system（CNS）,characterized by multiple demyelinating plaques in the white matter.For decades,the focus of MS research has been on inflammation-mediated demyelination of the white matter.

Release of interleukin-10 and neurotrophic factors in the choroid plexus：possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia

Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus（CP） is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors（brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3） and cytokines（tumor necrosis factor alpha, interferon-gamma, interleukin-4（IL-4）, IL-10 and IL-17）, in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.