Stroke affects intestinal immune cell trafficking to the central nervous system

Abstract Recent case studies show that the SARS-CoV-2 infectious disease, COVID-19, is associated with accelerated decline of mental health, in particular, cognition in elderly individuals, but also with neurological and neuropsychiatric illness in young people. Recent studies also show a bidirectional link between COVID-19 and mental health in that people with previous history of psychiatric illness have a higher risk for contracting COVID-19 and that COVID-19 patients display a variety of psychiatric illnesses. Risk factors and the response of the central nervous system to the virus show large overlaps with pathophysiological processes associated with Alzheimer’s disease, delirium, post-operative cognitive dysfunction and acute disseminated encephalomyelitis, all characterized by cognitive impairment. These similarities lead to the hypothesis that the neurological symptoms could arise from neuroinflammation and immune cell dysfunction both in the periphery as well as in the central nervous system and the assumption that long-term consequences of COVID-19 may lead to cognitive impairment in the well-being of the patient and thus in today’s workforce, resulting in large loss of productivity. Therefore, particular attention should be paid to neurological protection during treatment and recovery of COVID-19, while cognitive consequences may require monitoring.

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Complement facilitates developmental microglial pruning of astrocyte and vascular networks

10.1101/2022.01.12.476001 ◽

2022 ◽

Author(s):

Gopalan Gnanaguru ◽

Steven J Tabor ◽

Kentaro Yuda ◽

Ryo Mukai ◽

Jörg Köhl ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Immune Cell ◽

Vascular Density ◽

Vascular Networks ◽

Vascular Patterning ◽

Vascular Growth ◽

Vascular Bed ◽

Retinal Microglia ◽

The Central Nervous System

Microglia, the resident immune cell of the central nervous system, play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. This current work resolves a previously unknown role for microglia in facilitating the developmental pruning of the astrocytic template resulting in a spatially organized retinal vascular bed. Mechanistically, our study identified that local microglial expression of complement (C)3 and C3aR is necessary for the regulation of astrocyte patterning and vascular growth during retinal development. Ablation of retinal microglia, loss of C3 or C3aR reduced developmental pruning and clearance of astrocytic bodies leading to increased astrocyte density leading to altered vascular patterning during retinal vascular development. This data demonstrates that C3/C3aR signaling is an important checkpoint required for the finetuning of vascular density during neuroretinal development.

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Physiological comparison of autologous and allogeneic cell implantation in the central nervous system: defining and regulating immune cell activity against mesenchymal and neural stem cell grafts

Placenta ◽

10.1016/j.placenta.2011.07.044 ◽

2011 ◽

Vol 32 ◽

pp. S330-S331

Author(s):

P. Ponsaerts

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Stem Cell ◽

Neural Stem Cell ◽

Immune Cell ◽

Cell Activity ◽

Allogeneic Cell ◽

The Central Nervous System ◽

Cell Implantation

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Molecular patterns from a human gut-derived Lactobacillus strain suppress pathogenic infiltration of leukocytes into the central nervous system

Journal of Neuroinflammation ◽

10.1186/s12974-020-01959-2 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

John Michael S. Sanchez ◽

Daniel J. Doty ◽

Ana Beatriz DePaula-Silva ◽

D. Garrett Brown ◽

Rickesha Bell ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Gut Microbiota ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Human Gut ◽

Chemokine Production ◽

The Central Nervous System ◽

Molecular Patterns

Abstract Background Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects 2.5 million people worldwide. Growing evidence suggests that perturbation of the gut microbiota, the dense collection of microorganisms that colonize the gastrointestinal tract, plays a functional role in MS. Indeed, specific gut-resident bacteria are altered in patients with MS compared to healthy individuals, and colonization of gnotobiotic mice with MS-associated microbiota exacerbates preclinical models of MS. However, defining the molecular mechanisms by which gut commensals can remotely affect the neuroinflammatory process remains a critical gap in the field. Methods We utilized monophasic experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice and relapse-remitting EAE in SJL/J mice to test the effects of the products from a human gut-derived commensal strain of Lactobacillus paracasei (Lb). Results We report that Lb can ameliorate preclinical murine models of MS with both prophylactic and therapeutic administrations. Lb ameliorates disease through a Toll-like receptor 2-dependent mechanism via its microbe-associated molecular patterns that can be detected in the systemic circulation, are sufficient to downregulate chemokine production, and can reduce immune cell infiltration into the central nervous system (CNS). In addition, alterations in the gut microbiota mediated by Lb-associated molecular patterns are sufficient to provide partial protection against neuroinflammatory diseases. Conclusions Local Lb modulation of the gut microbiota and the shedding of Lb-associated molecular patterns into the circulation may be important physiological signals to prevent aberrant peripheral immune cell infiltration into the CNS and have relevance to the development of new therapeutic strategies for MS.

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