Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery
AbstractPast studies have observed that brain atrophy may accelerate after surgical procedures. Furthermore, an association of systemic inflammation with neurodegeneration has been described. We hypothesize that postoperative interleukin (IL) levels in circulation as well as the perioperative change in interleukin levels are associated with increased postoperative atrophy in the Nucleus basalis magnocellularis (of Meynert, NBM) which is the major source of cortical acetylcholine.  We analyzed data from the BioCog cohort which included patients ≥ 65 years presenting for elective major surgery (≥ 60min). Blood sam...
Source: Journal of NeuroImmune Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Source Type: research

Activation of the CXCR4 Receptor by Chemokine CXCL12 Increases the Excitability of Neurons in the Rat Central Amygdala
AbstractPrimarily regarded as immune proteins, chemokines are emerging as a family of molecules serving neuromodulatory functions in the developing and adult brain. Among them, CXCL12 is constitutively and widely expressed in the CNS, where it was shown to act on cellular, synaptic, network, and behavioral levels. Its receptor, CXCR4, is abundant in the amygdala, a brain structure involved in pathophysiology of anxiety disorders. Dysregulation of CXCL12/CXCR4 signaling has been implicated in anxiety-related behaviors. Here we demonstrate that exogenous CXCL12 at 2 nM but not at 5 nM increased neuronal excitability in the l...
Source: Journal of NeuroImmune Pharmacology - March 2, 2024 Category: Drugs & Pharmacology Source Type: research

Complement C3 From Astrocytes Plays Significant Roles in Sustained Activation of Microglia and Cognitive Dysfunctions Triggered by Systemic Inflammation After Laparotomy in Adult Male Mice
In this study, we investigated the role of C3 in mediating activation of microglia and cognitive dysfunction by using laparotomy in adult male mouse only as the experimental model of systemic inflammation and AAV9-C3shRN A. Our data observed that laparotomy induced neurotoxic reactive astrocytes with an increase of C3 in the hippocampus. Furthermore, inhibition of C3 by AAV9-C3shRNA prevented synaptic engulfment by microglia and attenuated cognitive dysfunctions after laparotomy. Inhibition of C3 did not modulate ac tivation of astrocytes and expression of various cytokines. Current findings demonstrated that C3 plays sign...
Source: Journal of NeuroImmune Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Source Type: research

New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation
AbstractInflammasomes are important modulators of inflammation. Dysregulation of inflammasomes can enhance vulnerability to conditions such as neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Among various inflammasomes, Nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) is the best-characterized inflammasome related to inflammatory and neurodegenerative diseases. NLRP3 is an intracellular sensor that recognizes pathogen-associated molecular patterns and damage-associated patterns resulting in the assembly and activation of NLRP3 inflam...
Source: Journal of NeuroImmune Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Source Type: research

TPN10475 Constrains Effector T Lymphocytes Activation and Attenuates Experimental Autoimmune Encephalomyelitis Pathogenesis by Facilitating TGF- β Signal Transduction
In this study, we aimed to investigate whether the artemisinin derivative TPN10475 could alleviate experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS and its possible mechanisms. TPN10475 effectively resisted the reduction of TGF- β signal transduction induced by TCR stimulation, suppressed the activation and function of effector CD4+ T cells in vitro, and restricted the differentiation of pathogenic Th1 and Th17 cells. It was also found to negatively regulate the inflammatory response in EAE by reducing the peripheral activation drive of auto-reactive helper T lymphocytes, inhibiting the ...
Source: Journal of NeuroImmune Pharmacology - February 27, 2024 Category: Drugs & Pharmacology Source Type: research

Heat Shock Protein 22 Attenuates Nerve Injury-induced Neuropathic Pain Via Improving Mitochondrial Biogenesis and Reducing Oxidative Stress Mediated By Spinal AMPK/PGC-1 α Pathway in Male Rats
In this study, pain behavioral test, western blotting, immunofluorescence staining, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Dihydroethidium staining are applied to confirm the role of hsp22 in a male rat model of spared nerve injury (SNI). Our results indicate that hsp22 was significantly decreased in spinal neurons post SNI. Moreover, it was found that intrathecal injection (i.t.) with recombinant heat shock protein 22 protein (rhsp22) ameliorated mechanical allodynia and thermal hyperalgesia, facilitated nuclear respiratory factor 1 (NRF1)/ mitochondrial transcription factor A (TFAM...
Source: Journal of NeuroImmune Pharmacology - February 6, 2024 Category: Drugs & Pharmacology Source Type: research

Potential Role of Bmal1 in Lipopolysaccharide-Induced Depression-Like Behavior and its Associated & quot;Inflammatory Storm & quot;
Conclusions In conclusion, our results indicated that LPS could induce depression-like behaviors and an “inflammatory storm” in vivo, activate microglia in vitro, together with a disruption of synaptic plasticity and circadian rhythm. This mechanism may be involved in the imbalanced expression of Bmal1. O ur results can help uncover a novel clock-immunological mechanism of neuroinflammation-induced depression and shed light on the development of new effective pharmacotherapies for depression (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - February 2, 2024 Category: Drugs & Pharmacology Source Type: research

VX-765 Alleviates Circadian Rhythm Disorder in a Rodent Model of Traumatic Brain Injury Plus Hemorrhagic Shock and Resuscitation
In conclusion, we sugge st that interventions targeting caspase-1-induced astrocytic pyroptosis by VX-765 are promising strategies to alleviate circadian rhythm disorder post-TBI.Graphical Abstract (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - February 1, 2024 Category: Drugs & Pharmacology Source Type: research

Doxycycline-Loaded Calcium Phosphate Nanoparticles with a Pectin Coat Can Ameliorate Lipopolysaccharide-Induced Neuroinflammation Via Enhancing AMPK
AbstractNeuroinflammation occurs in response to different injurious triggers to limit their hazardous effects. However, failure to stop this process can end in multiple neurological diseases. Doxycycline (DX) is a tetracycline, with potential antioxidant and anti-inflammatory properties. The current study tested the effects of free DX, DX-loaded calcium phosphate (DX@CaP), and pectin-coated DX@CaP (Pec/DX@CaP) nanoparticles on the lipopolysaccharide (LPS)-induced neuroinflammation in mice and to identify the role of adenosine monophosphate-activated protein kinase (AMPK) in this effect. The present study was conducted on 4...
Source: Journal of NeuroImmune Pharmacology - January 18, 2024 Category: Drugs & Pharmacology Source Type: research

Alleviating CB2-Dependent ER Stress and Mitochondrial Dysfunction Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment
AbstractAugmentation of endoplasmic reticulum (ER) stress may trigger excessive oxidative stress, which induces mitochondrial dysfunction. The fatty acid amide hydrolase inhibitor, URB597, shows anti-oxidation characteristics in multiple neurological disorders. The present study aimed to determine whether inhibition of ER stress was involved in the protective effects of URB597 against chronic cerebral hypoperfusion (CCH)-induced cognitive impairment. Hippocampal HT-22 cells were exposed to oxygen-glucose deprivation. The cell viability, apoptosis, ER stress, mitochondrial ATP, and oxidative stress levels were assessed foll...
Source: Journal of NeuroImmune Pharmacology - January 12, 2024 Category: Drugs & Pharmacology Source Type: research

Peripheral MC1R Activation Modulates Immune Responses and is Neuroprotective in a Mouse Model of Parkinson ’s Disease
ConclusionsOur study demonstrates that peripherally acting NDP-MSH confers protection on dopaminergic nigrostriatal neurons and reduces hyperactivated microglia. NDP-MSH modulates peripheral immune responses, and Tregs may be involved in the neuroprotective effect of NDP-MSH. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - December 19, 2023 Category: Drugs & Pharmacology Source Type: research

β-Sitosterol Alleviates Neuropathic Pain by Affect Microglia Polarization through Inhibiting TLR4/NF-κB Signaling Pathway
AbstractThe etiology of neuropathic pain is mostly caused by mechanical deformation and neuroinflammation, of which neuroinflammation is the main cause of chronic neuropathic pain. Activation of the TLR4/NF- κB signaling pathway mediates elevated levels of inflammatory cytokines, and we clearly demonstrated by in vivo and in vitro Western blot experiments that β-sitosterol significantly inhibited the elevated Toll-like receptor 4 (TLR4) expression levels and nuclear factor-kappa B (NF-κB) activation associated with inflammatory responses. In cellular experiments, we clearly saw that both β-sitosterol and TLR4/NF-κB si...
Source: Journal of NeuroImmune Pharmacology - December 2, 2023 Category: Drugs & Pharmacology Source Type: research

Low-dose IL-2 Treatment Rescues Cognitive Deficits by Repairing the Imbalance Between Treg and Th17 Cells at the Middle Alzheimer ’s Disease Stage
AbstractMultiple studies highlight the role of effector and regulatory CD4+T cells in the pathophysiology of Alzheimer ’s disease, and foster low-dose IL-2 treatment which induces regulatory CD4+T (Treg) cells expansion and activation as a promising strategy for its treatment. However, studies demonstrating discrepant Treg functions in AD have been reported. In addition, a compromised immune system associated with aging may substantially impact on these processes. Here, we report that there is an altered balance of activity between Treg cells and IL-17-producing helper T (Th17) cells in periphery and brain of APP/PS1 mic...
Source: Journal of NeuroImmune Pharmacology - November 14, 2023 Category: Drugs & Pharmacology Source Type: research

Sertraline Pre-Treatment Attenuates Hemorrhagic Transformation Induced in Rats after Cerebral Ischemia Reperfusion via Down Regulation of Neuronal CD163: Involvement of M1/M2 Polarization Interchange and Inhibiting Autophagy
In conclusion, Sert protected against cerebral I/R damage by attenuating oxidative stress, inflammation, autophagy, and apoptotic process. It is worth mentioning that our study was the first to show that Sert inhibited hemorrhagic transformation.Graphical AbstractThe protective effect of sertraline against injury induced by cerebral ischemia reperfusion via inhibiting Hemorrhagic transformation. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - November 13, 2023 Category: Drugs & Pharmacology Source Type: research

Edaravone Confers Neuroprotective, Anti-inflammatory, and Antioxidant Effects on the Fetal Brain of a Placental-ischemia Mouse Model
In conclusion, RUPP-placental ischemia mouse model could be a useful tool to further understand the underlying mechanisms of PE-induced child neuronal alterations. Edaravone could be a potential adjuvant therapy during PE to protect the developing fetal brain.Graphical AbstractThe current study investigated the effects of a placenta-induced ischemia mouse model using reduced uterine perfusion pressure (RUPP) surgery on the fetal brain development and the potential neuroprotective effects of the drug edaravone. The study found that the RUPP model caused neurodegeneration and a pro-inflammatory response in the developing fet...
Source: Journal of NeuroImmune Pharmacology - November 4, 2023 Category: Drugs & Pharmacology Source Type: research