Neuroprotective Action of Teriflunomide in a Mouse Model of Transient Middle Cerebral Artery Occlusion

Lu, Zhaoming; Zhang, Di; Cui, Kefei; Fu, Xiaojie; Jiang, Man; Lü, Hong; Yu, Lie; Gao, Yufeng; Xian-liang, Liu; Liao, Linghui; Li, Xiang; Liu, Chang; Zhang, Yongxin; Zhang, Zhen; Wang, Jianping

doi:10.1016/j.neuroscience.2019.12.011

Cited by 17 publications

(15 citation statements)

References 43 publications

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“…At high concentrations, TF diminished the LPS-and IFN-γ induced CD68 expression in vitro [258], and following LPS stimulation, the expression of the M2 microglia cytokine IL-10 was slightly increased in rat primary microglia and mixed glial cultures [258]. Furthermore, TF decreased the expression of the pro-inflammatory cytokines CXCL10, CCL2 and IL-6 in human microglia-monocyte co-cultures stimulated with HIV particles [146], and lower levels of the pro-inflammatory proteins IL-1β, COX2 and 3-NT were detected following the TF treatment of mice with tMCAO-induced stroke [254]. However, in primary rat microglia cultures, no effect of TF was observed on the mRNA expression levels of iNOS, IL-6 and TNFα and on the protein level of NFκB inhibitor IκBα [258].…”

Section: Microgliamentioning

confidence: 93%

“…Axonal loss was also diminished by TF in the CNS of TMEV-demyelination mice [257]. In addition, TF treatment stimulated neurogenesis in the hippocampal sub granular zone of TBI rats [256], and upregulated the number of BrdU-/DCX-positive cells and the expression of mammalian achaete-schute homolog 1 (MASH1), DCX and PBX homeobox 1 (PBX1) in the sub ventricular zone of the mouse tMCAO stroke model [254]. In vitro, the neurotoxic effect of the medium from HIV-particle-stimulated microglia-monocytes co-cultures on human fetal neurons was attenuated by TF [146].…”

Section: Neuronsmentioning

confidence: 98%

“…Another peripheral effect of TF concerns the decrease in pro-inflammatory IL release from monocytes [253]. In the brain, TF reduced BBB damage by increasing the number of pericytes, and the levels of the tight-junction proteins Zonula occludens protein-1 (ZO-1) and occludin (OCLN) [254]. Moreover, in the brain, TF targets circulating levels of pyrimidine and purine nucleotides, and of GSH and carbohydrate metabolism intermediates [255].…”

Section: Molecular Effects Of Tfmentioning

confidence: 99%

“…A reduction in the number of pro-inflammatory M1 Sialoadhesin (SIGLEC-1)-positive or IBA1-positive microglia following TF treatment has been reported in rodent models for various diseases, such as in the brains of mice suffering from neuronal ceroid lipofuscinosis (CLN) [49], in the hippocampus of two different rat models for traumatic brain injury (TBI) [256], in the basal ganglia and the corpus callosum of a Theiler's murine encephalomyelitis virus (TMEV)-induced mouse demyelination model [257], and fewer IBA1-positive cells were also detected in the brains of transient middle cerebral artery occlusion (tMCAO) stroke mice [254]. At high concentrations, TF diminished the LPS-and IFN-γ induced CD68 expression in vitro [258], and following LPS stimulation, the expression of the M2 microglia cytokine IL-10 was slightly increased in rat primary microglia and mixed glial cultures [258].…”

Section: Microgliamentioning

confidence: 99%

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Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Kleijn

Martens

2020

IJMS

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Multiple sclerosis (MS) is characterized by peripheral and central inflammatory features, as well as demyelination and neurodegeneration. The available Food and Drug Administration (FDA)-approved drugs for MS have been designed to suppress the peripheral immune system. In addition, however, the effects of these drugs may be partially attributed to their influence on glial cells and neurons of the central nervous system (CNS). We here describe the molecular effects of the traditional and more recent FDA-approved MS drugs Fingolimod, Dimethyl Fumarate, Glatiramer Acetate, Interferon-β, Teriflunomide, Laquinimod, Natalizumab, Alemtuzumab and Ocrelizumab on microglia, astrocytes, neurons and oligodendrocytes. Furthermore, we point to a possible common molecular effect of these drugs, namely a key role for NFκB signaling, causing a switch from pro-inflammatory microglia and astrocytes to anti-inflammatory phenotypes of these CNS cell types that recently emerged as central players in MS pathogenesis. This notion argues for the need to further explore the molecular mechanisms underlying MS drug action.

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Section: Microgliamentioning

confidence: 93%

Section: Neuronsmentioning

confidence: 98%

Section: Molecular Effects Of Tfmentioning

confidence: 99%

Section: Microgliamentioning

confidence: 99%

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Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Kleijn

Martens

2020

IJMS

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“…In a mouse model where ECs, SMCs, and PCs partly lack guanylyl cyclase B, the endothelial C‐type natriuretic peptide acts on PCs, thereby regulating microcirculatory flow and blood pressure 107 . Additionally, teriflunomide improves pericyte coverage and survival, resulting in decreased TJ protein breakdown and BBB leakage 108 . A recent study has shown that novel interpericyte tunneling nanotubes could build a functional network to regulate neurovascular coupling through linking two separate PCs on different capillaries in the mouse retina 109 …”

Section: Is Therapies Targeting the Nvumentioning

confidence: 99%

Neurovascular Unit: A critical role in ischemic stroke

et al. 2021

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Ischemic stroke (IS), a common cerebrovascular disease, results from a sudden blockage of a blood vessel in the brain, thereby restricting blood supply to the area in question, and making a significantly negative impact on human health. Unfortunately, current treatments, that are mainly based on a recanalization of occluded blood vessels, are insufficient or inaccessible to many stroke patients. Recently, the profound influence of the neurovascular unit (NVU) on recanalization and the prognosis of IS have become better understood; in‐depth studies of the NVU have also provided novel approaches for IS treatment. In this article, we review the intimate connections between the changes in the NVU and IS outcomes, and discuss possible new management strategies having practical significance to IS. We discuss the concept of the NVU, as well as its roles in IS blood‐brain barrier regulation, cell preservation, inflammatory immune response, and neurovascular repair. Besides, we also summarize the influence of noncoding RNAs in NVU, and IS therapies targeting the NVU. We conclude that both the pathophysiological and neurovascular repair processes of IS are strongly associated with the homeostatic state of the NVU and that further research into therapies directed at the NVU could expand the range of treatments available for IS.

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Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

Islam

Leach

Smith³

et al. 2021

Advanced Science

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The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease is known to be increasing due to an aging population and is anticipated to further grow in the decades ahead. The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. An increasingly important observation is that the physiology of the brain alters during many brain diseases, and aging adds even more to the complexity of the disease. There is a notion that the permeability of the blood–brain barrier (BBB) increases with aging or disease, however, the body has a defense mechanism that still retains the separation of the brain from harmful chemicals in the blood. This makes drug delivery to the diseased brain, even more challenging and complex task. Here, the physiological changes to the diseased brain and aged brain are covered in the context of drug delivery to the brain using nanoparticles. Also, recent and novel approaches are discussed for the delivery of therapeutic agents to the diseased brain using nanoparticle based or magnetic resonance imaging guided systems. Furthermore, the complement activation, toxicity, and immunogenicity of brain targeting nanoparticles as well as novel in vitro BBB models are discussed.

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Neuroprotective Action of Teriflunomide in a Mouse Model of Transient Middle Cerebral Artery Occlusion

Cited by 17 publications

References 43 publications

Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Neurovascular Unit: A critical role in ischemic stroke

Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

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