Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Metabolic Brain Disease
Published in: Metabolic Brain Disease 4/2019

01-08-2019 | Laminectomy | Original Article

Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination

Authors: Mahboubeh Mousavi, Azim Hedayatpour, Keywan Mortezaee, Yousef Mohamadi, Farid Abolhassani, Gholamreza Hassanzadeh

Published in: Metabolic Brain Disease | Issue 4/2019

Login to get access

Abstract

Inflammasome activation in the traumatic central nervous system (CNS) injuries is responsible for propagation of an inflammatory circuit and neuronal cell death resulting in sensory/motor deficiencies. NLRP1 and NLRP3 are known as activators of inflammasome complex in the spinal cord injury (SCI). In this study, cell therapy using Schwann cells (SCs) was applied for targeting NLRP inflammasome complexes outcomes in the motor recovery. These cells were chosen due to their regenerative roles for CNS injuries. SCs were isolated from sciatic nerves and transplanted to the contusive SCI-induced Wistar rats. NLRP1 and NLRP3 inflammasome complexes and their related pro-inflammatory cytokines were assayed in both mRNA and protein levels. Neuronal cell survival (Nissl staining), motor recovery and myelination (Luxol fast blue/LFB) were also evaluated. The groups were laminectomy, SCI, vehicle and treatment. The treatment group received Schwann cells, and the vehicle group received solvent for the cells. SCI caused increased expressions for both NLRP1 and NLRP3 inflammasome complexes along with their related pro-inflammatory cytokines, all of which were abrogated after administration of SCs (except for IL-18 protein showing no change to the cell therapy). Motor deficits in the hind limb, neuronal cell death and demyelination were also found in the SCI group, which were counteracted in the treatment group. From our findings we conclude promising role for cell therapy with SCs for targeting axonal demyelination and degeneration possibly through attenuation of the activity for inflammasome complexes and related inflammatory circuit.
Literature
Anderson DK, Means ED, Waters TR, Green ES (1982) Microvascular perfusion and metabolism in injured spinal cord after methylprednisolone treatment. J Neurosurg 56:106–113CrossRefPubMed
Arthur-Farraj PJ et al (2012) C-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron 75:633–647CrossRefPubMedPubMedCentral
Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244–256CrossRefPubMed
Bazley FA et al (2012) Electrophysiological evaluation of sensory and motor pathways after incomplete unilateral spinal cord contusion. J Neurosurg Spine 16:414–423CrossRefPubMed
Bazrafkan M et al (2018) Lipid peroxidation and its role in the expression of NLRP1a and NLRP3 genes in testicular tissue of male rats: a model of spinal cord injury. Iran Biomed J 22:151PubMedPubMedCentral
Chen L, Huang H, Xi H, Zhang F, Liu Y, Chen D, Xiao J (2014) A prospective randomized double-blind clinical trial using a combination of olfactory ensheathing cells and Schwann cells for the treatment of chronic complete spinal cord injuries. Cell Transplant 23:35–44CrossRef
Choobineh H, Gilani MAS, Pasalar P, Jahanzad I, Ghorbani R, Hassanzadeh G (2016) The effects of testosterone on oxidative stress markers in mice with spinal cord injuries. Int J Fertility Sterility 10:87
Choobineh H, Kazemi M, Gilani MAS, Heydari T, Shokri S, Bazrafkan M, Hassanzadeh G (2018) Testosterone reduces spinal cord injury-induced effects on male reproduction by preventing CADM1. Defect Cell J (Yakhteh) 20:138
Cocco M et al (2017) Development of an acrylate derivative targeting the NLRP3 Inflammasome for the treatment of. Inflammatory Bowel Disease J Medicinal Chemistry 60:3656–3671
De la Calle JL, Paı́no CL (2002) A procedure for direct lumbar puncture in rats. Brain Res Bull 59:245–250CrossRefPubMed
de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW (2008) A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci 28:3404–3414CrossRefPubMedPubMedCentral
de Rivero Vaccari JP, Lotocki G, Alonso OF, Bramlett HM, Dietrich WD, Keane RW (2009) Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J Cereb Blood Flow Metab 29:1251–1261CrossRefPubMedPubMedCentral
Deng L-X et al (2013) A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury. J Neurosci 33:5655–5667CrossRefPubMedPubMedCentral
Deng L-X, Walker C, Xu X-M (2015) Schwann cell transplantation and descending propriospinal regeneration after spinal cord injury. Brain Res 1619:104–114CrossRefPubMed
Dubový P (2011) Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction. Annals of Anatomy-Anatomischer Anzeiger 193:267–275CrossRef
Fleshner M, Frank M, Maier SF (2017) Danger signals and inflammasomes: stress-evoked sterile inflammation in mood disorders. Neuropsychopharmacology 42:36CrossRefPubMed
Gholaminejhad M, Arabzadeh S, Akbari M, Mohamadi Y, Hassanzadeh G (2017) Anti-oxidative and neuroprotective effects of flaxseed on experimental unilateral spinal cord injury in rat. J Contemporary Med Sci 3:213–217CrossRef
Gong W, Mao S, Yu J, Song J, Jia Z, Huang S, Zhang A (2016) NLRP3 deletion protects against renal fibrosis and attenuates mitochondrial abnormality in mouse with 5/6 nephrectomy. American J Physiology-Renal Physiology 310:F1081–F1088CrossRef
Grace PM et al (2016) Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc Natl Acad Sci 113:E3441–E3450CrossRefPubMed
Hassanzadeh G, Quchani SH, Sahraian MA, Abolhassani F, Gilani MAS, Tarzjani MD, Atoof F (2016) Leukocyte gene expression and plasma concentration in multiple sclerosis: alteration of transforming growth factor-βs, Claudin-11, and matrix Metalloproteinase-2. Cell Mol Neurobiol 36:865–872CrossRefPubMed
Hsu L-C et al (2008) A NOD2–NALP1 complex mediates caspase-1-dependent IL-1β secretion in response to bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci 105:7803–7808CrossRefPubMed
Jiang W et al (2016a) Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury. Spinal Cord 54:592–596CrossRefPubMed
Jiang W et al (2016b) Dopamine D1 receptor agonist A-68930 inhibits NLRP3 inflammasome activation, controls inflammation, and alleviates histopathology in a rat model of spinal cord injury. Spine 41:E330–E334CrossRefPubMed
Jiang W et al (2016c) Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci 157:45–51CrossRefPubMed
Kachadroka S, Hall AM, Niedzielko TL, Chongthammakun S, Floyd CL (2010) Effect of endogenous androgens on 17 β-estradiol-mediated protection after spinal cord injury in male rats. J Neurotrauma 27:611–626CrossRefPubMedPubMedCentral
Kang MJ, Jo SG, Kim DJ, Park JH (2017) NLRP3 inflammasome mediates interleukin-1β production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice. Immunology 150:495–505CrossRefPubMedPubMedCentral
Kreider B, Messing A, Doan H, Kim S, Lisak R, Pleasure D (1981) Enrichment of Schwann cell cultures from neonatal rat sciatic nerve by differential adhesion. Brain Res 207:433–444CrossRefPubMed
Kuo H-S et al (2011) Acid fibroblast growth factor and peripheral nerve grafts regulate Th2 cytokine expression, macrophage activation, polyamine synthesis, and neurotrophin expression in transected rat spinal cords. J Neurosci 31:4137–4147CrossRefPubMedPubMedCentral
Lan Z, Xie G, Wei M, Wang P, Chen L (2017) The protective effect of Epimedii folium and Curculiginis Rhizoma on Alzheimer’s disease by the inhibitions of NF-κB/MAPK pathway and NLRP3 inflammasome. Oncotarget 8:43709PubMedPubMedCentral
Lavdas AA, Chen J, Papastefanaki F, Chen S, Schachner M, Matsas R, Thomaidou D (2010) Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury. Exp Neurol 221:206–216CrossRefPubMed
Liang F, Li C, Gao C, Li Z, Yang J, Liu X, Wang Y (2015) Effects of hyperbaric oxygen therapy on NACHT domain-leucine-rich-repeat-and pyrin domain-containing protein 3 inflammasome expression in rats following spinal cord injury. Mol Med Rep 11:4650–4656CrossRefPubMed
Liu H-D et al (2013) Expression of the NLRP3 inflammasome in cerebral cortex after traumatic brain injury in a rat model. Neurochem Res 38:2072–2083CrossRefPubMed
Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell 10:417–426CrossRefPubMed
Mirsky R et al (2002) Schwann cells as regulators of nerve development. J Physiology-Paris 96:17–24CrossRef
Mortazavi MM, Harmon OA, Adeeb N, Deep A, Tubbs RS (2015) Treatment of spinal cord injury: a review of engineering using neural and mesenchymal stem cells. Clin Anat 28:37–44CrossRefPubMed
Mortezaee K, Khanlarkhani N, Beyer C, Zendedel A (2018) Inflammasome: its role in traumatic brain and spinal cord injury. J Cell Physiol 233:5160–5169CrossRefPubMed
Myers SA, Bankston AN, Burke DA, Ohri SS, Whittemore SR (2016) Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials? Exp Neurol 283:560–572CrossRefPubMedPubMedCentral
Nikmehr B et al (2017) The correlation of gene expression of inflammasome indicators and impaired fertility in rat model of spinal cord injury: a time course study. Urol J 14:5057–5063PubMed
Norenberg MD, Smith J, Marcillo A (2004) The pathology of human spinal cord injury: defining the problems. Mary Ann Liebert, Inc
Oraee-Yazdani S et al (2016) Co-transplantation of autologous bone marrow mesenchymal stem cells and Schwann cells through cerebral spinal fluid for the treatment of patients with chronic spinal cord injury: safety and possible outcome. Spinal Cord 54:102–109CrossRefPubMed
Petrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J (2007) Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ 14:1583CrossRefPubMed
Pineau I, Sun L, Bastien D, Lacroix S (2010) Astrocytes initiate inflammation in the injured mouse spinal cord by promoting the entry of neutrophils and inflammatory monocytes in an IL-1 receptor/MyD88-dependent fashion. Brain Behav Immun 24:540–553CrossRefPubMed
Pishva AA et al (2016) Effect of estrogen therapy on TNF-α and iNOS gene expression in spinal cord injury model. Acta medica Iranica 54:296–301
Profyris C, Cheema SS, Zang D, Azari MF, Boyle K, Petratos S (2004) Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiol Dis 15:415–436CrossRefPubMed
Qian J, Zhu W, Lu M, Ni B, Yang J (2017) D-β-hydroxybutyrate promotes functional recovery and relieves pain hypersensitivity in mice with spinal cord injury. Br J Pharmacol 174:1961–1971CrossRefPubMedPubMedCentral
Rice T, Larsen J, Rivest S, Yong VW (2007) Characterization of the early neuroinflammation after spinal cord injury in mice. J Neuropathol Exp Neurol 66:184–195CrossRefPubMed
Saberi H et al (2011) Safety of intramedullary Schwann cell transplantation for postrehabilitation spinal cord injuries: 2-year follow-up of 33 cases. J Neurosurg Spine 15:515–525CrossRefPubMed
Sekhon LH, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 26:S2–S12CrossRefPubMed
Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-α, interleukin-1α, and interleukin-1β. J Neurosci 22:3052–3060CrossRefPubMed
Shen A et al (2008) Lipopolysaccharide-evoked activation of p38 and JNK leads to an increase in ICAM-1 expression in Schwann cells of sciatic nerves. FEBS J 275:4343–4353CrossRefPubMed
Taskinen H, Olsson T, Bucht A, Khademi M, Svelander L, Röyttä M (2000) Peripheral nerve injury induces endoneurial expression of IFN-γ, IL-10 and TNF-α mRNA. J Neuroimmunol 102:17–25CrossRefPubMed
Tillakaratne NJ et al (2010) Functional recovery of stepping in rats after a complete neonatal spinal cord transection is not due to regrowth across the lesion site. Neuroscience 166:23–33CrossRefPubMed
Tofaris GK, Patterson PH, Jessen KR, Mirsky R (2002) Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J Neurosci 22:6696–6703CrossRefPubMed
Tschopp J, Schroder K (2010) NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 10:210CrossRefPubMed
Zendedel A, Johann S, Mehrabi S, M-t J, Hassanzadeh G, Kipp M, Beyer C (2016) Activation and regulation of NLRP3 inflammasome by intrathecal application of SDF-1a in a spinal cord injury model. Mol Neurobiol 53:3063–3075CrossRefPubMed
Zhang K-J, Zhang H-L, Zhang X-M, Zheng X-Y, Quezada HC, Zhang D, Zhu J (2011) Apolipoprotein E isoform-specific effects on cytokine and nitric oxide production from mouse Schwann cells after inflammatory stimulation. Neurosci Lett 499:175–180CrossRefPubMed
Zhang H-Y et al (2013) Regulation of autophagy and ubiquitinated protein accumulation by bFGF promotes functional recovery and neural protection in a rat model of spinal cord injury. Mol Neurobiol 48:452–464CrossRefPubMed
Zhou X-H et al (2012) Transplantation of autologous activated Schwann cells in the treatment of spinal cord injury: six cases, more than five years of follow-up. Cell Transplant 21:S39–S47CrossRefPubMed
Zhu Y, Zhu H, Wang Z, Gao F, Wang J, Zhang W (2017) Wogonoside alleviates inflammation induced by traumatic spinal cord injury by suppressing NF-κB and NLRP3 inflammasome activation. Experimental and Therapeutic Medicine 14:3304–3308CrossRefPubMedPubMedCentral
Metadata
Title
Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination
Authors
Mahboubeh Mousavi
Azim Hedayatpour
Keywan Mortezaee
Yousef Mohamadi
Farid Abolhassani
Gholamreza Hassanzadeh
Publication date
01-08-2019
Publisher
Springer US
Keyword
Laminectomy
Published in
Metabolic Brain Disease / Issue 4/2019
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-019-00433-0

Other articles of this Issue 4/2019

Metabolic Brain Disease 4/2019 Go to the issue

Original Article

Rutin alleviates cadmium-induced neurotoxicity in Wistar rats: involvement of modulation of nucleotide-degrading enzymes and monoamine oxidase

Original Article

Neuroprotective effect of diclofenac on chlorpromazine induced catalepsy in rats

Original Article

Autosomal dominant optic atrophy plus due to the novel OPA1 variant c.1463G>C

Original Article

Metabolic stroke in a patient with bi-allelic OPA1 mutations

Original Article

Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase activity, Ca2+ influx and inflammatory cytokine molecular pathways in the docetaxel-treated mice by melatonin and selenium treatments

Review Article

Association between polymorphisms of NOS1, NOS2 and NOS3 genes and suicide behavior: a systematic review and meta-analysis