scholarly journals Interleukin-1 and the Interleukin-1 Type 1 Receptor are Essential for the Progressive Neurodegeneration that Ensues Subsequent to a Mild Hypoxic/Ischemic Injury

2005 ◽  
Vol 25 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Anirban Basu ◽  
Jelena Lazovic ◽  
J Kyle Krady ◽  
David T Mauger ◽  
Raymond P Rothstein ◽  
...  
Keyword(s):  
Brain Damage ◽  
Proinflammatory Cytokine ◽  
Microglial Activation ◽  
Neurological Diseases ◽  
Interleukin 1 ◽  
Progressive Neurodegeneration ◽  
Extent Of Damage ◽  
The Brain ◽  
Progressive Enlargement

Excessive inflammation has been implicated in the progressive neurodegeneration that occurs in multiple neurological diseases, including cerebral ischemia, and elevated levels of the proinflammatory cytokine interleukin-1 (IL-1) have been shown to exacerbate brain damage, whereas diminishing IL-1 levels limits the extent of injury. However, to date there is no consensus regarding which receptor(s) mediates the detrimental effects of IL-1. Because we have previously demonstrated that signaling through the IL-1 type 1 receptor (IL-1R1) is necessary for microglial activation and because results from other studies have implicated microglia as effectors of neurodegeneration, we hypothesized that inactivating the IL-1R1 would decrease the extent of damage caused by a hypoxic-ischemic (H/I) insult. It is shown that a mild insult initiates progressive neurodegeneration that leads to cystic infarcts, which can be prevented by inactivating the IL-1R1. The IL-1R1 null mice also show preserved sensorimotor function at 1 month's recovery. The mild insult induces multiple proinflammatory cytokines and activates microglia, and these responses are dramatically curtailed in mice lacking the IL-1R1. Importantly, the neuroinflammation precedes the progressive enlargement of the infarct, suggesting that the inflammation is causal rather than a consequence of the brain damage. These findings show that abrogating the inflammation consequent to a mild H/I insult will prevent brain damage and preserve neurological function. Additionally, these data incriminate the IL-1R1 as a master proinflammatory cytokine receptor.

scholarly journals A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Luiza A. Castro-Jorge ◽  
Carla D. Pretto ◽  
Asa B. Smith ◽  
Oded Foreman ◽  
Kelly E. Carnahan ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Time Course ◽  
Interleukin 1 ◽  
Adenovirus Type ◽  
Mouse Strains ◽  
Complex Nature ◽  
Type I ◽  
Viral Loads ◽  
The Brain

ABSTRACT Interleukin-1β (IL-1β), an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor (Il1r1 −/− mice). Il1r1 −/− mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL/6J mice. We also examined infections of mice defective in IL-1β production (Pycard −/− mice) and mice defective in trafficking of Toll-like receptors to the endosome (Unc93b1 −/− mice). Pycard −/− and Unc93b1 −/− mice showed lower survival (similar to Il1r1 −/− mice) than control mice but, unlike Il1r1 −/− mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected Unc93b1 −/− mice had a very different inflammatory profile from infected Il1r1 −/− and Pycard −/− mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in Il1r1 −/− mice. A time course of infection of control and Il1r1 −/− mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-β signaling may result in increased neuroinflammation. IMPORTANCE The investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis.

scholarly journals Brain Perivascular Macrophages Do Not Mediate Interleukin-1-Induced Sickness Behavior in Rats

2021 ◽  
Vol 14 (10) ◽  
pp. 1030
Author(s):  
Léa Chaskiel ◽  
Robert Dantzer ◽  
Jan Konsman
Keyword(s):  
Social Interactions ◽  
Interleukin 1 ◽  
Sickness Behavior ◽  
Behavioral Activity ◽  
Activated Macrophages ◽  
Perivascular Macrophages ◽  
The Brain ◽  
Do So

Sickness behavior, characterized by on overall reduction in behavioral activity, is commonly observed after bacterial infection. Sickness behavior can also be induced by the peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. In addition to the microglia, the brain contains perivascular macrophages, which express the IL-1 type 1 receptor (IL-1R1). In the present study, we assessed the role of brain perivascular macrophages in mediating IL-1β-induced sickness behavior in rats. To do so, we used intracerebroventricular (icv) administration of an IL-1β-saporin conjugate, known to eliminate IL-R1-expressing brain cells, prior to systemic or central IL-1β injection. Icv IL-1β-saporin administration resulted in a reduction in brain perivascular macrophages, without altering subsequent icv or ip IL-1β-induced reductions in food intake, locomotor activity, and social interactions. In conclusion, the present work shows that icv IL-1β-saporin administration is an efficient way to target brain perivascular macrophages, and to determine whether these cells are involved in IL-1β-induced sickness behavior.

scholarly journals ASTROCYTES AND THEIR ROLE IN THE PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM

2019 ◽  
Vol 21 (1) ◽  
pp. 46-53
Author(s):  
L. R. Gorbacheva ◽  
I. A. Pomytkin ◽  
A. M. Surin ◽  
E. A. Abramov ◽  
Vsevolod G. Pinelis
Keyword(s):  
Glial Cells ◽  
Brain Injuries ◽  
Negative Impact ◽  
Neurological Diseases ◽  
Clinical Neurology ◽  
Actual Problem ◽  
Functional Changes ◽  
Repair Mechanisms ◽  
Progressive Neurodegeneration ◽  
The Brain

Determination of the structural-functional significance of astrocytes in the physiology and pathology of the CNS is an actual problem of modern neuroscience and clinical neurology. Astrocytes are glial cells of the brain, constitute the substance of the brain, support neurons and separate them with their bodies into compartments. They participate in the immune response of the brain, they are able to maintain the chronic inflammation and progressive neurodegeneration due to overexpression of cytokines, growth factors, and chemokines. This review discusses the key features of astrogliosis as complex of molecular, cellular and functional changes of astrocytes in the response to various brain injuries. Reactive astrogliosis is critical for regeneration and remodeling of neural networks after the injury and ischemia and can have both positive and negative impact. The overexpression of S100b protein is an index of the astrocyte activation, which is characteristic for glial cells as this protein is located mainly in astrocytes. In cerebral ischemia, traumatic brain injury or neurodegenerative diseases there is the modulation of astrogliosis, aimed at the provision of repair mechanisms of the damaged parts of the brain that determines search capabilities of the new means of pharmacological correction of activated astrocytes and other glial components for the treatment of neurological diseases.

Preferential involvement of Na+/Ca2+ exchanger type-1 in the brain damage caused by transient focal cerebral ischemia in mice

2012 ◽  
Vol 429 (3-4) ◽  
pp. 186-190 ◽  
Author(s):  
Nobutaka Morimoto ◽  
Satomi Kita ◽  
Masamitsu Shimazawa ◽  
Hiroko Namimatsu ◽  
Kazuhiro Tsuruma ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Transient Focal Cerebral Ischemia ◽  
The Brain

Effects of phosphodiesterase inhibitors on cytokine production by microglia

1999 ◽  
Vol 5 (2) ◽  
pp. 126-133 ◽  
Author(s):  
Minka Yoshikawa ◽  
Akio Suzumura ◽  
Tsukasa Tamaru ◽  
Tetsuya Takayanagi ◽  
Makato Sawada
Keyword(s):  
Neurological Diseases ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Critical Role ◽  
Phosphodiesterase Inhibitors ◽  
Dependent Manner ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Pass Through

Type III and IV phosphodiesterase inhibitors (PDEIs) have recently been shown to suppress the production of TNF-α in several types of cells. In the present study, we have shown that all the types of PDEIs, from type 1- to V-specific and non-specific, suppress the production of TNF-α by mouse microglia stimulated with lipopolysaccharide (LPS) in a dose-dependent manner. Certain combinations of three different types of PDEIs synergistically suppressed TNF-α production by microglia at a very low concentration (1 μM). Since some PDEIs reportedly pass through the blood-brain barrier (BBB), the combination of three PDEIs may be worth trying in neurological diseases, such as multiple sclerosis and HIV-related neurological diseases in which TNF-α may play a critical role. Some PDEIs also suppressed interleukin-1 (IL-1) and IL-6 production by mouse microglia stimulated with LPS. In contrast, the production of IL-10, which is known to be an inhibitory cytokine, was upregulated by certain PDEIs. The suppression of TNF-α and induction of IL-10 were confirmed at the mRNA level by RT - PCR. PDEIs may be useful anti-inflammatory agents by downregulating inflammatory cytokines and upregulating inhibitory cytokines in the central nervous system. (CNS).

Rehabilitation of Attention

2003 ◽  
Vol 14 (3) ◽  
pp. 165-170 ◽  
Author(s):  
Ian H. Robertson
Keyword(s):  
Brain Damage ◽  
Dependent Plasticity ◽  
Attention Systems ◽  
The Brain

Abstract: In this paper, evidence is reviewed for separable attention systems in the brain, and it is argued a) that attention may have a privileged role in mediating experience dependent plasticity in the brain and b) that at least some types of attention may be capable of rehabilitation following brain damage.

Neuro-Optometric Treatment of Complications from a Cerebellar Astrocytoma

2020 ◽  
pp. 304-312
Keyword(s):  
Visual System ◽  
Common Site ◽  
Us Army ◽  
Cranial Nerve Palsies ◽  
Pilocytic Astrocytomas ◽  
The Us ◽  
Extent Of Damage ◽  
Functional Components ◽  
The Brain

Background: Insult to the brain, whether from trauma or other etiologies, can have a devastating effect on an individual. Symptoms can be many and varied, depending on the location and extent of damage. This presentation can be a challenge to the optometrist charged with treating the sequelae of this event as multiple functional components of the visual system can be affected. Case Report: This paper describes the diagnosis and subsequent ophthalmic management of an acquired brain injury in a 22 year old male on active duty in the US Army. After developing acute neurological symptoms, the patient was diagnosed with a pilocytic astrocytoma of the cerebellum. Emergent neurosurgery to treat the neoplasm resulted in iatrogenic cranial nerve palsies and a hemispheric syndrome. Over the next 18 months, he was managed by a series of providers, including a strabismus surgeon, until presenting to our clinic. Lenses, prism, and in-office and out-of-office neurooptometric rehabilitation therapy were utilized to improve his functioning and make progress towards his goals. Conclusions: Pilocytic astrocytomas are the most common primary brain tumors, and the vast majority are benign with excellent surgical prognosis. Although the most common site is the cerebellum, the visual pathway is also frequently affected. If the eye or visual system is affected, optometrists have the ability to drastically improve quality of life with neuro-optometric rehabilitation.

Aetiologies and anatomy of confabulation

2017 ◽  
Author(s):  
Armin Schnider
Keyword(s):  
Brain Damage ◽  
Limbic Encephalitis ◽  
Artery Aneurysm ◽  
Anterior Communicating Artery ◽  
Brain Areas ◽  
Anatomical Basis ◽  
Korsakoff Syndrome ◽  
Hypoxic Brain ◽  
Degenerative Dementia ◽  
The Brain

What diseases cause confabulations and which are the brain areas whose damage is responsible? This chapter reviews the causes, both historic and present, of confabulations and deduces the anatomo-clinical relationships for the four forms of confabulation in the following disorders: alcoholic Korsakoff syndrome, traumatic brain injury, rupture of an anterior communicating artery aneurysm, posterior circulation stroke, herpes and limbic encephalitis, hypoxic brain damage, degenerative dementia, tumours, schizophrenia, and syphilis. Overall, clinically relevant confabulation is rare. Some aetiologies have become more important over time, others have virtually disappeared. While confabulations seem to be more frequent after anterior brain damage, only one form has a distinct anatomical basis.

scholarly journals Molecular mechanisms of metabotropic GABAB receptor function

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3362
Author(s):  
Hamidreza Shaye ◽  
Benjamin Stauch ◽  
Cornelius Gati ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Neurological Diseases ◽  
Activation Mechanism ◽  
Allosteric Modulators ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Drugs ◽  
G Protein Coupled ◽  
The Brain

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

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