Neuroimmune system

Neuroimmune system
Neuroimmune system
	This diagram depicts the neuroimmune mechanisms that mediate methamphetamine-induced neurodegeneration in the human brain. The NF-κB-mediated neuroimmune response to methamphetamine use which results in the increased permeability of the blood–brain barrier arises through its binding at and activation of sigma-1 receptors, the increased production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and damage-associated molecular pattern molecules (DAMPs), the dysregulation of glutamate transporters (specifically, EAAT1 and EAAT2) and glucose metabolism, and excessive calcium influx in glial cells and dopamine neurons.
Details
System	Neuroimmune
Identifiers
MeSH	D015213
	Anatomical terminology

The neuroimmune system is a system of structures and processes involving the biochemical and electrophysiological interactions between the nervous system and immune system which protect neurons from pathogens. It serves to protect neurons against disease by maintaining selectively permeable barriers (e.g., the blood–brain barrier and blood–cerebrospinal fluid barrier), mediating neuroinflammation and wound healing in damaged neurons, and mobilizing host defenses against pathogens.^[2]^[4]^[5]

The neuroimmune system and peripheral immune system are structurally distinct. Unlike the peripheral system, the neuroimmune system is composed primarily of glial cells;^[1]^[5] among all the hematopoietic cells of the immune system, only mast cells are normally present in the neuroimmune system.^[6] However, during a neuroimmune response, certain peripheral immune cells are able to cross various blood or fluid–brain barriers in order to respond to pathogens that have entered the brain.^[2] For example, there is evidence that following injury macrophages and T cells of the immune system migrate into the spinal cord.^[7] Production of immune cells of the complement system have also been documented as being created directly in the central nervous system.^[8]

^ ^a ^b ^c Beardsley PM, Hauser KF (2014). "Glial Modulators as Potential Treatments of Psychostimulant Abuse". Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Advances in Pharmacology. Vol. 69. pp. 1–69. doi:10.1016/B978-0-12-420118-7.00001-9. ISBN 9780124201187. PMC 4103010. PMID 24484974. Glia (including astrocytes, microglia, and oligodendrocytes), which constitute the majority of cells in the brain, have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants
^ ^a ^b ^c Loftis JM, Janowsky A (2014). "Neuroimmune Basis of Methamphetamine Toxicity". Neuroimmune Signaling in Drug Actions and Addictions. International Review of Neurobiology. Vol. 118. pp. 165–197. doi:10.1016/B978-0-12-801284-0.00007-5. ISBN 9780128012840. PMC 4418472. PMID 25175865. Collectively, these pathological processes contribute to neurotoxicity (e.g., increased BBB permeability, inflammation, neuronal degeneration, cell death) and neuropsychiatric impairments (e.g., cognitive deficits, mood disorders) {{cite book}}: |journal= ignored (help)
"Figure 7.1: Neuroimmune mechanisms of methamphetamine-induced CNS toxicity"
^ Kaushal N, Matsumoto RR (March 2011). "Role of sigma receptors in methamphetamine-induced neurotoxicity". Curr Neuropharmacol. 9 (1): 54–57. doi:10.2174/157015911795016930. PMC 3137201. PMID 21886562.
^ Cite error: The named reference Neuroimmune receptors was invoked but never defined (see the help page).
^ ^a ^b Cite error: The named reference Astrocytes - abundant neuroimmune cells was invoked but never defined (see the help page).
^ Cite error: The named reference Mast cell neuroimmmune system was invoked but never defined (see the help page).
^ Ji, Ru-Rong; Xu, Zhen-Zhong; Gao, Yong-Jing (2014). "Emerging targets in neuroinflammation-driven chronic pain". Nature Reviews Drug Discovery. 13 (7): 533–548. doi:10.1038/nrd4334. PMC 4228377. PMID 24948120.
^ Stephan, Alexander H.; Barres, Ben A.; Stevens, Beth (2012-01-01). "The Complement System: An Unexpected Role in Synaptic Pruning During Development and Disease". Annual Review of Neuroscience. 35 (1): 369–389. doi:10.1146/annurev-neuro-061010-113810. PMID 22715882. S2CID 2309037.

[Glial_tox_review_-_Ntox_diagram-1] Beardsley PM, Hauser KF (2014). "Glial Modulators as Potential Treatments of Psychostimulant Abuse". Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Advances in Pharmacology. Vol. 69. pp. 1–69. doi:10.1016/B978-0-12-420118-7.00001-9. ISBN 9780124201187. PMC 4103010. PMID 24484974. Glia (including astrocytes, microglia, and oligodendrocytes), which constitute the majority of cells in the brain, have many of the same receptors as neurons, secrete neurotransmitters and neurotrophic and neuroinflammatory factors, control clearance of neurotransmitters from synaptic clefts, and are intimately involved in synaptic plasticity. Despite their prevalence and spectrum of functions, appreciation of their potential general importance has been elusive since their identification in the mid-1800s, and only relatively recently have they been gaining their due respect. This development of appreciation has been nurtured by the growing awareness that drugs of abuse, including the psychostimulants, affect glial activity, and glial activity, in turn, has been found to modulate the effects of the psychostimulants

[Neuroimmune_meth_toxicity-2] Loftis JM, Janowsky A (2014). "Neuroimmune Basis of Methamphetamine Toxicity". Neuroimmune Signaling in Drug Actions and Addictions. International Review of Neurobiology. Vol. 118. pp. 165–197. doi:10.1016/B978-0-12-801284-0.00007-5. ISBN 9780128012840. PMC 4418472. PMID 25175865. Collectively, these pathological processes contribute to neurotoxicity (e.g., increased BBB permeability, inflammation, neuronal degeneration, cell death) and neuropsychiatric impairments (e.g., cognitive deficits, mood disorders) {{cite book}}: |journal= ignored (help)
"Figure 7.1: Neuroimmune mechanisms of methamphetamine-induced CNS toxicity"

[Sigma-3] Kaushal N, Matsumoto RR (March 2011). "Role of sigma receptors in methamphetamine-induced neurotoxicity". Curr Neuropharmacol. 9 (1): 54–57. doi:10.2174/157015911795016930. PMC 3137201. PMID 21886562.

[Neuroimmune_receptors-4] Cite error: The named reference Neuroimmune receptors was invoked but never defined (see the help page).

[Astrocytes_-_abundant_neuroimmune_cells-5] Cite error: The named reference Astrocytes - abundant neuroimmune cells was invoked but never defined (see the help page).

[Mast_cell_neuroimmmune_system-6] Cite error: The named reference Mast cell neuroimmmune system was invoked but never defined (see the help page).

[:1-7] Ji, Ru-Rong; Xu, Zhen-Zhong; Gao, Yong-Jing (2014). "Emerging targets in neuroinflammation-driven chronic pain". Nature Reviews Drug Discovery. 13 (7): 533–548. doi:10.1038/nrd4334. PMC 4228377. PMID 24948120.

[8] Stephan, Alexander H.; Barres, Ben A.; Stevens, Beth (2012-01-01). "The Complement System: An Unexpected Role in Synaptic Pruning During Development and Disease". Annual Review of Neuroscience. 35 (1): 369–389. doi:10.1146/annurev-neuro-061010-113810. PMID 22715882. S2CID 2309037.

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