scholarly journals Combination Treatment of C16 Peptide and Angiopoietin-1 Alleviates Neuromyelitis Optica in an Experimental Model

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Kewei Tian ◽  
Hong Jiang ◽  
Beibei Wang ◽  
Shu Han
Keyword(s):  
Neuromyelitis Optica ◽  
Inflammatory Cell ◽  
Demyelinating Disease ◽  
Neuronal Damage ◽  
Binding Peptide ◽  
Complement Dependent Cytotoxicity ◽  
Secondary Demyelination ◽  
Inflammatory Milieu ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease that mainly affects the spinal cord and optic nerve, causing blindness and paralysis in some individuals. Moreover, NMO may cause secondary complement-dependent cytotoxicity (CDC), leading to oligodendrocyte and neuronal damage. In this study, a rodent NMO model, showing typical NMO pathogenesis, was induced with NMO-IgG from patient serum and human complement. We then tested whether the combination of C16, an αvβ3 integrin-binding peptide, and angiopoietin-1 (Ang1), a member of the endothelial growth factor family, could alleviate NMO in the model. Our results demonstrated that this combination therapy significantly decreased disease severity, inflammatory cell infiltration, secondary demyelination, and axonal loss, thus reducing neural death. In conclusion, our study suggests a possible treatment that can relieve progressive blindness and paralysis in an animal model of NMO through improvement of the inflammatory milieu.

scholarly journals Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
S. Viswanathan ◽  
N. Rose ◽  
A. Masita ◽  
J. S. Dhaliwal ◽  
S. D. Puvanarajah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Age At Onset ◽  
Positive Family History ◽  
Disease Onset ◽  
Demyelinating Diseases ◽  
Lesion Length ◽  
Relapsing Remitting ◽  
Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

scholarly journals Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica

2008 ◽  
Vol 66 (3b) ◽  
pp. 678-684 ◽  
Author(s):  
Soniza Vieira Alves-Leon ◽  
Maria Lucia Vellutini Pimentel ◽  
Gabrielle Sant'Anna ◽  
Fabíola Rachid Malfetano ◽  
Cláudio Duque Estrada ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
B Lymphocyte ◽  
Demyelinating Disease ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Control Group ◽  
Regulatory Cells ◽  
Immunological Parameters ◽  
Healthy Control ◽  
The Central Nervous System

Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-γ (INF-γ) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (p<0.0001), PLP (p=0.0002) and MBP (p<0.0001), and solely IgA to MBP (p<0.0001). INF-γ (p=0.61) levels were similar to healthy controls. Increased production of IL-4 (p=0.0084) indicates an important role for this cytokine in the activation of Th2 regulatory cells and of the IgA producers B lymphocyte indicating activation of humoral immunity.

scholarly journals Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

2013 ◽  
Vol 71 (5) ◽  
pp. 275-279 ◽  
Author(s):  
Denis Bernardi Bichuetti ◽  
Enedina Maria Lobato de Oliveira ◽  
Nilton Amorin de Souza ◽  
Mar Tintoré ◽  
Alberto Alain Gabbai
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Disease Duration ◽  
Demyelinating Disease ◽  
Age Of Onset ◽  
Severe Disease ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Although neuromyelitis optica (NMO) is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS), few studies comparing both conditions in a single center have been done.Methods:Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007.Results:Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062) with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013) and progression index (0.9 versus 0.6, p≪0.0001), with more patients reaching expanded disability status scale (EDSS) 6.0 (39 versus 17%, p=0.0036). The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15.Conclusion:Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

Angiopoietin-1 promotes lymphatic sprouting and hyperplasia

Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4642-4648 ◽  
Author(s):  
Tuomas Tammela ◽  
Anne Saaristo ◽  
Marja Lohela ◽  
Tohru Morisada ◽  
Jenny Tornberg ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Viral Vectors ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Soluble Form ◽  
Tissue Edema ◽  
Mouse Tissues ◽  
Vessel Development ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

Abstract Angiopoietin 1 (Ang1), a ligand for the receptor tyrosine kinase Tie2, regulates the formation and stabilization of the blood vessel network during embryogenesis. In adults, Ang1 is associated with blood vessel stabilization and recruitment of perivascular cells, whereas Ang2 acts to counter these actions. Recent results from gene-targeted mice have shown that Ang2 is also essential for the proper patterning of lymphatic vessels and that Ang1 can be substituted for this function. In order to characterize the effects of the angiopoietins on lymphatic vessels, we employed viral vectors for overexpression of Ang1 in adult mouse tissues. We found that Ang1 activated lymphatic vessel endothelial proliferation, vessel enlargement, and generation of long endothelial cell filopodia that eventually fused, leading to new sprouts and vessel development. Cutaneous lymphatic hyperplasia was also detected in transgenic mice expressing Ang1 in the basal epidermal cells. Tie2 was expressed in the lymphatic endothelial cells and Ang1 stimulation of these cells resulted in up-regulation of vascular endothelial growth factor receptor 3 (VEGFR-3). Furthermore, a soluble form of VEGFR-3 inhibited the observed lymphatic sprouting. Our results reinforce the concept that Ang1 therapy may be useful in settings of tissue edema. (Blood. 2005;105:4642-4648)

scholarly journals Role of Vascular Endothelial Growth Factor and Angiopoietin 1 in Renal Injury in Hemolytic Uremic Syndrome

2012 ◽  
Vol 36 (6) ◽  
pp. 516-523 ◽  
Author(s):  
Shinichiro Ohara ◽  
Yukihiko Kawasaki ◽  
Yusaku Abe ◽  
Masahiro Watanabe ◽  
Atsushi Ono ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hemolytic Uremic Syndrome ◽  
Renal Injury ◽  
Vascular Endothelial ◽  
Uremic Syndrome ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

scholarly journals Perspective of SGLT2 Inhibition in Treatment of Conditions Connected to Neuronal Loss: Focus on Alzheimer’s Disease and Ischemia-Related Brain Injury

2020 ◽  
Vol 13 (11) ◽  
pp. 379
Author(s):  
Michał Wiciński ◽  
Eryk Wódkiewicz ◽  
Karol Górski ◽  
Maciej Walczak ◽  
Bartosz Malinowski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Damage ◽  
Neurovascular Unit ◽  
Neuronal Loss ◽  
Impact Risk ◽  
Sglt2 Inhibition ◽  
The Central Nervous System ◽  
Cortical Regions ◽  
Endothelial Growth Factor

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are oral anti-hyperglycemic agents approved for the treatment of type 2 diabetes mellitus. Some reports suggest their presence in the central nervous system and possible neuroprotective properties. SGLT2 inhibition by empagliflozin has shown to reduce amyloid burden in cortical regions of APP/PS1xd/db mice. The same effect was noticed regarding tau pathology and brain atrophy volume. Empagliflozin presented beneficial effect on cognitive function, which may be connected to an increase in cerebral brain-derived neurotrophic factor. Canagliflozin and dapagliflozin may possess acetylcholinesterase inhibiting activity, resembling in this matter Alzheimer’s disease-registered therapies. SGLT2 inhibitors may prove to impact risk factors of atherosclerosis and pathways participating both in acute and late stage of stroke. Their mechanism of action can be related to induction in hepatocyte nuclear factor-1α, vascular endothelial growth factor-A, and proinflammatory factors limitation. Empagliflozin may have a positive effect on preservation of neurovascular unit in diabetic mice, preventing its aberrant remodeling. Canagliflozin seems to present some cytostatic properties by limiting both human and mice endothelial cells proliferation. The paper presents potential mechanisms of SGLT-2 inhibitors in conditions connected with neuronal damage, with special emphasis on Alzheimer’s disease and cerebral ischemia.

scholarly journals Impact of heat therapy on recovery after eccentric exercise in humans

2019 ◽  
Vol 126 (4) ◽  
pp. 965-976 ◽  
Author(s):  
Kyoungrae Kim ◽  
Shihuan Kuang ◽  
Qifan Song ◽  
Timothy P. Gavin ◽  
Bruno T. Roseguini
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Fatigue Resistance ◽  
Eccentric Exercise ◽  
Knee Extensors ◽  
Vascular Endothelial ◽  
Heat Therapy ◽  
Endothelial Growth Factor ◽  
Exercise In Humans ◽  
Angiopoietin 1

The purpose of this study was to investigate the effects of heat therapy (HT) on functional recovery, the skeletal muscle expression of angiogenic factors, macrophage content, and capillarization after eccentric exercise in humans. Eleven untrained individuals (23.8 ± 0.6 yr) performed 300 bilateral maximal eccentric contractions of the knee extensors. One randomly selected thigh was treated with five daily 90-min sessions of HT, whereas the opposite thigh received a thermoneutral intervention. Peak isokinetic torque of the knee extensors was assessed at baseline and daily for 4 days and fatigue resistance was assessed at baseline and 1 and 4 days after the eccentric exercise session. Muscle biopsies were obtained 2 wk before and 1 and 5 days after the eccentric exercise bout. There were no differences between thighs in the overall recovery profile of peak torque. However, the thigh exposed to HT had greater fatigue resistance than the thigh exposed to the thermoneutral intervention. The change from baseline in mRNA expression of vascular endothelial growth factor (VEGF) was higher at day 1 in the thigh exposed to HT. Protein levels of VEGF and angiopoietin 1 were also significantly higher in the thigh treated with HT. The number of capillaries around type II fibers decreased similarly in both thighs at day 5. Exposure to HT had no impact on macrophage content. These results suggest that HT accelerates the recovery of fatigue resistance after eccentric exercise and promotes the expression of angiogenic factors in human skeletal muscle. NEW & NOTEWORTHY We investigated whether exposure to local heat therapy (HT) accelerates recovery after a bout of eccentric exercise in humans. Compared with a thermoneutral control intervention, HT improved fatigue resistance of the knee extensors and enhanced the expression of the angiogenic mediators vascular endothelial growth factor and angiopoietin 1. These results suggest that HT hastens functional recovery and enhances the expression of regulatory factors involved in muscle repair after eccentric exercise in humans.

Sign in / Sign up

Export Citation Format

Share Document