scholarly journals The discovery of natalizumab, a potent therapeutic for multiple sclerosis

2012 ◽  
Vol 199 (3) ◽  
pp. 413-416 ◽  
Author(s):  
Lawrence Steinman
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Immune Cells ◽  
Strong Evidence ◽  
Demyelinating Disease ◽  
Critical Component ◽  
The Central Nervous System ◽  
The Brain

Multiple sclerosis (MS) is the major inflammatory demyelinating disease of the central nervous system. There is strong evidence that an immune response in the brain is a critical component of the disease. In 1992, in a collaboration between academia and biotechnology, my colleagues and I showed that α4 integrin was the critical molecule involved in the homing of immune cells into the inflamed brain. Was it sheer luck that these results led to the development of a drug for MS?

scholarly journals Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Genaro G. Ortiz ◽  
Fermín P. Pacheco-Moisés ◽  
Oscar K. Bitzer-Quintero ◽  
Ana C. Ramírez-Anguiano ◽  
Luis J. Flores-Alvarado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Tissue Injury ◽  
Autoimmune Disorder ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
The Brain ◽  
And Oxidative Stress

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

scholarly journals What Guides Peripheral Immune Cells into the Central Nervous System?

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2041
Author(s):  
Theresa Greiner ◽  
Markus Kipp
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cells ◽  
Progressive Disease ◽  
Demyelinating Disease ◽  
Disease Stage ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Peripheral Immune Cells

Multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system (CNS), initially presents with a relapsing-remitting disease course. During this early stage of the disease, leukocytes cross the blood–brain barrier to drive the formation of focal demyelinating plaques. Disease-modifying agents that modulate or suppress the peripheral immune system provide a therapeutic benefit during relapsing-remitting MS (RRMS). The majority of individuals with RRMS ultimately enter a secondary progressive disease stage with a progressive accumulation of neurologic deficits. The cellular and molecular basis for this transition is unclear and the role of inflammation during the secondary progressive disease stage is a subject of intense and controversial debate. In this review article, we discuss the following main hypothesis: during both disease stages, peripheral immune cells are triggered by CNS-intrinsic stimuli to invade the brain parenchyma. Furthermore, we outline the different neuroanatomical routes by which peripheral immune cells might migrate from the periphery into the CNS.

scholarly journals Blood serum amino acids profile in patients with Multiple Sclerosis

2015 ◽  
Vol 26 (1) ◽  
pp. 50-53
Keyword(s):  
Multiple Sclerosis ◽  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Blood Serum ◽  
Demyelinating Disease ◽  
Initial Step ◽  
Control Group ◽  
The Central Nervous System ◽  
Amino Acids Profile

Multiple sclerosis is the most common demyelinating disease of the central nervous system, affecting mostly young people. There were many risk factors for MS identified, however a direct cause of the disease is still unknown. Pathological changes in the SM lead to the myelin sheath damage around axons, what prevents proper transmission of nerve impulses in the central nervous system. The aim of this study was analyzing and comparing the amino acids profile in the blood serum of MS patients to control group of healthy individuals and evaluating the relationship between them. Significant (p<0.05) differences in the level of glutamate, aspartate and taurine in the blood serum of MS patients were revealed. A positive glutamate and aspartate level correlation in the serum has been demonstrated. Gender is significant only in the case of glutamate level in blood serum. The studies highlight the important role of neurotransmitters in MS and are the initial step in proteomic research.

scholarly journals Multiple Sclerosis

2020 ◽  
Author(s):  
Amirhossein Azari Jafari ◽  
Seyyedmohammadsadeq Mirmoeeni
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Autoimmune Disease ◽  
The Central Nervous System ◽  
Genetic And Environmental Factors ◽  
Chronic Autoimmune Disease ◽  
The Brain

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS), caused by genetic and environmental factors. It is characterized by intermittent and recurrent episodes of inflammation that result in the demyelination and subsequent damage of the underlying axons present in the brain, optic nerve and spinal cord [1][2][3].

Microglia and the Brain: Complementary Partners in Development and Disease

2018 ◽  
Vol 34 (1) ◽  
pp. 523-544 ◽  
Author(s):  
Timothy R. Hammond ◽  
Daisy Robinton ◽  
Beth Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Disease ◽  
Immune Cells ◽  
New Technologies ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Synaptic Maturation ◽  
The Brain ◽  
Normal Brain Development

An explosion of findings driven by powerful new technologies has expanded our understanding of microglia, the resident immune cells of the central nervous system (CNS). This wave of discoveries has fueled a growing interest in the roles that these cells play in the development of the CNS and in the neuropathology of a diverse array of disorders. In this review, we discuss the crucial roles that microglia play in shaping the brain—from their influence on neurons and glia within the developing CNS to their roles in synaptic maturation and brain wiring—as well as some of the obstacles to overcome when assessing their contributions to normal brain development. Furthermore, we examine how normal developmental functions of microglia are perturbed or remerge in neurodevelopmental and neurodegenerative disease.

Movement Disorders

2016 ◽  
pp. 619-624
Author(s):  
Anhar Hassan ◽  
Eduardo E. Benarroch
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Young Adults ◽  
Movement Disorders ◽  
Demyelinating Disease ◽  
Substantial Effect ◽  
The Central Nervous System

The most common inflammatory demyelinating disease of the central nervous system is multiple sclerosis, a disabling disorder that affects predominantly young adults between 20 and 50 years old. It affects women twice as often as men. Multiple sclerosis has a complex immunopathogenesis, variable prognosis, and an unpredictable course. Polygenic and environmental (possibly viral) factors probably have a substantial effect on susceptibility to multiple sclerosis.

scholarly journals Erythrocytes in multiple sclerosis – forgotten contributors to the pathophysiology?

2016 ◽  
Vol 2 ◽  
pp. 205521731664998
Author(s):  
Kira Groen ◽  
Vicki E Maltby ◽  
Katherine A Sanders ◽  
Rodney J Scott ◽  
Lotti Tajouri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Genetic Predisposition ◽  
Immune Cells ◽  
Lymphocytic Infiltration ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an autoimmune disease characterised by lymphocytic infiltration of the central nervous system and subsequent destruction of myelin and axons. On the background of a genetic predisposition to autoimmunity, environmental triggers are assumed to initiate the disease. The majority of MS research has focused on the pathological involvement of lymphocytes and other immune cells, yet a paucity of attention has been given to erythrocytes, which may play an important role in MS pathology. The following review briefly summarises how erythrocytes may contribute to MS pathology through impaired antioxidant capacity and altered haemorheological features. The effect of disease-modifying therapies on erythrocytes is also reviewed. It may be important to further investigate erythrocytes in MS, as this could broaden the understanding of the pathological mechanisms of the disease, as well as potentially lead to the discovery of novel and innovative targets for future therapies.

scholarly journals Spread and Replication of and Immune Response to γ134.5-Negative Herpes Simplex Virus Type 1 Vectors in BALB/c Mice

2004 ◽  
Vol 78 (23) ◽  
pp. 13139-13152 ◽  
Author(s):  
Eeva K. Broberg ◽  
Jutta Peltoniemi ◽  
Michaela Nygårdas ◽  
Tero Vahlberg ◽  
Matias Röyttä ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Herpes Simplex ◽  
Trigeminal Ganglia ◽  
Rt Pcr ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

ABSTRACT We have previously shown that intracranial infection of herpes simplex virus type 1 (HSV-1) vector R8306 expressing interleukin-4 (IL-4) can abolish symptoms of experimental autoimmune encephalomyelitis, which is used as a model for human multiple sclerosis (Broberg et al., Gene Ther. 8:769-777, 2001). The aim of the current study was to search for means other than intracranial injection to deliver HSV-derived vectors to the central nervous system of mice. We also aimed to study the replication efficiency of these vectors in nervous system tissues and to elucidate the effects of the viruses on the immune response. We studied the spread and replication of the following viruses with deletions in neurovirulence gene γ134.5: R3616, R849 (lacZ transgene), R3659 (alpha-tk), R8306 (murine IL-4 transgene), and R8308 (murine IL-10 transgene). The samples were taken from trigeminal ganglia and brains of BALB/c mice after corneal, intralabial, and intranasal infection, and the viral load was examined by viral culture, HSV DNA PCR, and VP16 reverse transcription (RT)-PCR. The results show that (i) intranasal infection was the most efficient means of spread to the central nervous system (CNS) besides intracranial injection; (ii) the viruses did not grow in the culture from the brain samples, but the viral DNA persisted even until day 21 postinfection; (iii) viral replication, as observed by VP16 mRNA RT-PCR, occurred mainly on days 4 and 7 postinfection in trigeminal ganglia and to a low extent in brain; (iv) R3659, R8306, and R8308 showed reactivation from the trigeminal ganglia in explant cultures; (v) in the brain, the vectors spread to the midbrain more efficiently than to other brain areas; and (vi) the deletions in the R3659 genome significantly limited the ability of this virus to replicate in the nervous system. The immunological studies show that (i) the only recombinant to induce IL-4 mRNA expression in the brain was R8306, the gamma interferon response was very low in the brain for R3659 and R8306, and the IL-23p19 response to R8306 decreased by day 21 postinfection, unlike for the other viruses; (ii) Δγ134.5 HSV vectors modulated the subsets of the splenocytes differently depending on the transgene; (iii) R3659 infection of the nervous system induces expression and production of cytokines from the stimulated splenocytes; and (iv) HSV vectors expressing IL-4 or IL-10 induce expression and production of both of the Th2-type cytokines from splenocytes. We conclude that the intranasal route of infection is a possible means of delivery of Δγ134.5 HSV vectors to the CNS in addition to intracranial infection, although replication in the CNS remains minimal. The DNA of the HSV vectors is able to reside in the brain for at least 3 weeks. The features of the immune response to the vectors must be considered and may be exploited in gene therapy experiments with these vectors.

Myricetin alleviates cuprizone-induced behavioral dysfunction and demyelination in mice by Nrf2 pathway

2016 ◽  
Vol 7 (10) ◽  
pp. 4332-4342 ◽  
Author(s):  
Qianying Zhang ◽  
Zhike Li ◽  
Shuangchan Wu ◽  
Xiaofei Li ◽  
Ying Sang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Nrf2 Pathway ◽  
Behavioral Dysfunction ◽  
System P ◽  
The Central Nervous System

Multiple sclerosis (MS) is a demyelinating disease occurring in the central nervous system.

scholarly journals COMBINATION OF MULTIPLE SCLEROSIS AND HEREDITARY OPTICAL LEBER’S NEUROPATHY. CLINICAL CASE

2021 ◽  
Vol 30 (4) ◽  
pp. 50-54
Author(s):  
Azalia Aisarovna Sokolova ◽  
◽  
Leonid Sergeevich Zemlyanushin ◽  
Elvira Aysarovna Vashkulatova ◽  
Sofia Mikhailovna Zemlyanushina
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Genetic Testing ◽  
Optic Nerve ◽  
Clinical Case ◽  
Demyelinating Disease ◽  
Mcdonald Criteria ◽  
The Central Nervous System ◽  
Hereditary Optic Atrophy

The article discusses a clinical case of demyelinating disease of the central nervous system, multiple sclerosis in combination with Leber’s hereditary optic atrophy of the optic nerve (Harding syndrome). The debut of the disease at the age of 24 in the form of a simultaneous bilateral decrease in vision, with subsequent atrophy of the optic nerves in both eyes. The diagnosis of multiple sclerosis was confi rmed according to the 2017 McDonald criteria, the diagnosis of Leber’s disease was confi rmed by genetic testing. An important point in the diff erential diagnosis was the identifi cation of the G3460A mutation in the ND1 gene and intrathecal synthesis of oligoclonal immunoglobulin G.

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