Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Inflammation as a Neurobiological Mechanism of Cognitive Impairment in Psychological Stress.

The feeling of emotional tension, restlessness, pressure, and inability to relax is referred to as psychological stress. Although it is unclear how psychological stress affects neurobiological processes, several factors are thought to be involved, including central and peripheral neuroinflammation, structural degeneration in the prefrontal cortex and hippocampus, alterations in fear neurocircuitry, and neuroplasticity. Aside from data relating cognitive impairment to chronic low-grade inflammatory stress, there is growing evidence linking mental stress, oxidative stress, and systemic inflammation to the development of psychological disorders. After chronic and acute illnesses, insomnia, depression, anxiety, posttraumatic stress disorder, and cognitive impairment were reported. Cognitive impairment is exacerbated by systemic and central inflammatory processes. There is uncertainty about the potential mechanisms causing these symptoms, although they are likely complex, with systemic inflammation playing a significant role. Therefore, this review aims to investigate the role of inflammation in stress-induced cognitive impairment. Depicting the inflammatory mechanisms of cognitive impairment is critical for understanding and treating illnesses, such as chronic stress exposure and anxiety disorders.

Potential convergence of olfactory dysfunction in Parkinson's disease and COVID-19: The role of neuroinflammation.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD.

Primary mitochondrial diseases: The intertwined pathophysiology of bioenergetic dysregulation, oxidative stress and neuroinflammation.

OBJECTIVES AND SCOPE: Primary mitochondrial diseases (PMDs) are rare genetic disorders resulting from mutations in genes crucial for effective oxidative phosphorylation (OXPHOS) that can affect mitochondrial function. In this review, we examine the bioenergetic alterations and oxidative stress observed in cellular models of primary mitochondrial diseases (PMDs), shedding light on the intricate complexity between mitochondrial dysfunction and cellular pathology. We explore the diverse cellular models utilized to study PMDs, including patient-derived fibroblasts, induced pluripotent stem cells (iPSCs) and cybrids. Moreover, we also emphasize the connection between oxidative stress and neuroinflammation. INSIGHTS: The central nervous system (CNS) is particularly vulnerable to mitochondrial dysfunction due to its dependence on aerobic metabolism and the correct functioning of OXPHOS. Similar to other neurodegenerative diseases affecting the CNS, individuals with PMDs exhibit several neuroinflammatory hallmarks alongside neurodegeneration, a pattern also extensively observed in mouse models of mitochondrial diseases. Based on histopathological analysis of postmortem human brain tissue and findings in mouse models of PMDs, we posit that neuroinflammation is not merely a consequence of neurodegeneration but a potential pathogenic mechanism for disease progression that deserves further investigation. This recognition may pave the way for novel therapeutic strategies for this group of devastating diseases that currently lack effective treatments. SUMMARY: In summary, this review provides a comprehensive overview of bioenergetic alterations and redox imbalance in cellular models of PMDs while underscoring the significance of neuroinflammation as a potential driver in disease progression.

Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats.

Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (p < 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (p < 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (<10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.

Simple and Complex Wheel Running Effect on Depression, Memory, Neuroinflammation, and Neurogenesis in Alzheimer's Rat Model.

INTRODUCTION: The aim of this study was to investigate 12 wk of simple and complex voluntary wheel running on Alzheimer's disease (AD), associated biomarkers, and behaviors. METHODS: Sixty male Wistar rats were randomly divided into six groups: healthy control (Con-Sed), AD only (AD-Sed), simple wheel control (SWC), complex wheel control (CWC), simple wheel AD (SWAD), and complex wheel AD (CWAD). Novelty-suppressed feeding test and the Morris water maze test were used to evaluate depression and memory, respectively. Ki67 was measured in the hippocampus, whereas interleukin (IL)-1ß and neural/glial antigen 2 (NG2) were measured in both the hippocampus and the prefrontal cortex. One-way ANOVA with Tukey's post hoc test was performed. RESULTS: AD-Sed group had significantly lower spacial memory ( P < 0.001) compared with Con-Sed. Simple and complex wheel running attenuated these deficits in the SWAD and CWAD groups, respectively ( P < 0.001). Only the CWAD group had significantly improved novelty-suppressed feeding test time compared with AD-Sed ( P < 0.001), equivalent to the healthy wheel running groups. AD-Sed has significantly higher hippocampal concentrations of Ki67 ( P = 0.01) compared with the Con-Sed. Both SWAD and CWAD had significantly reduced Ki67 with similar concentrations compared with the SWC and CWC groups ( P > 0.05). AD-Sed animals also presented with significantly higher hippocampal and prefrontal cortex concentrations of IL-1ß compared with Con-Sed ( P < 0.001). SWAD and CWAD had no effect in changing these concentrations. Complex wheel running significantly increased NG2 in the healthy control and AD models, whereas simple wheel running significantly increased NG2 in the AD model. CONCLUSIONS: The results of our study suggest that complex wheel running might be more advantageous in promoting memory and neuroplasticity while reducing depression that is associated with AD.

Efectos de inducción recíproca entre periodontitis e hiposalivación: revisión de la literatura / Reciprocal induction effects between periodontitis and hyposalivation: a review of the literature

Muchas investigaciones se han ocupado de evaluar la vinculación entre las afecciones bucales y otras funciones o afecciones del organismo. Algunos de esos estudios han sentado precedentes acerca de la influencia mutua que puede existir entre la fun-cionalidad de las glándulas salivales y la enfermedad periodontal, y cómo la presencia de una condición puede modificar la evolución o inducir la aparición de la otra. El objetivo del presente trabajo es hacer una revisión bibliográfica de las publicaciones cientí-ficas que evalúan los efectos de inducción recíproca que existe entre la enfermedad periodontal y la hi-posalivación. Trabajos de nuestro grupo y de otros autores demuestran que la hiposalivación reduce la capacidad del organismo para defenderse contra las bacterias patógenas, mantener un ambiente sa-ludable y facilitar la cicatrización en la cavidad bu-cal, promoviendo los procesos de inflamación y daño tisular gingivoperiodontal. A su vez, varios estudios reportan que la enfermedad periodontal induce cam-bios en las glándulas salivales y altera el volumen de secreción salival. Por su parte, el sistema endo-cannabinoide (SEC) muestra estar involucrado tanto en el proceso de secreción salival como en la infla-mación y la reabsorción ósea presentes en la enfer-medad periodontal, en tanto que la activación de los mecanismos del SEC emerge como una de las vías a través de las cuales se desarrollaría el fenómeno de inducción recíproca (AU)

Many investigations have focused on evaluating the link between oral conditions and other functions or conditions of the body. Some of these studies have set precedents about the mutual influence that may exist between the functionality of the salivary glands and periodontal disease, and how the presence of one condition can modify the evolution or induce the appearance of the other. The objective of this work is to carry out a bibliographic review of scientific publications that evaluate the reciprocal induction effects that exist between periodontal disease and hyposalivation. Studies by our group and other authors show that hyposalivation reduces the capacity of the organism to defend itself against pathogenic bacteria, maintain a healthy environment and facilitate healing in the oral cavity, promoting inflammation and gingivoperiodontal tissue damage. In turn, several studies report that periodontal disease induces changes in the salivary glands and alters the volume of salivary secretion. In turn, the endocannabinoid system (ECS) is shown to be involved in the salivary secretion process as well as in the inflammation and bone resorption present in periodontal disease, while the activation of ECS mechanisms emerges as one of the pathways through which the reciprocal induction phenomenon would develop (AU)

Focal mu-opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain.

Microglia participates in the modulation of pain signaling. The activation of microglia is suggested to play an important role in affective disorders that are related to a dysfunction of the mesocorticolimbic system (MCLS) and are commonly associated with chronic pain. Moreover, there is evidence that mu-opioid receptors (MORs), expressed in the MCLS, are involved in neuroinflammatory events, although the way by which they do it remains to be elucidated. In this study, we propose that MOR pharmacological activation within the MCLS activates and triggers the local release of proinflammatory cytokines and this pattern of activation is impacted by the presence of systemic inflammatory pain. To test this hypothesis, we used in vivo microdialysis coupled with flow cytometry to measure cytokines release in the nucleus accumbens and immunofluorescence of IBA1 in areas of the MCLS on a rat model of inflammatory pain. Interestingly, the treatment with DAMGO, a MOR agonist locally in the nucleus accumbens, triggered the release of the IL1α, IL1ß, and IL6 proinflammatory cytokines. Furthermore, MOR pharmacological activation in the ventral tegmental area (VTA) modified the levels of IBA1-positive cells in the VTA, prefrontal cortex, the nucleus accumbens and the amygdala in a dose-dependent way, without impacting mechanical nociception. Additionally, MOR blockade in the VTA prevents DAMGO-induced effects. Finally, we observed that systemic inflammatory pain altered the IBA1 immunostaining derived from MOR activation in the MSCLS. Altogether, our results indicate that the microglia-MOR relationship could be pivotal to unravel some inflammatory pain-induced comorbidities related to MCLS dysfunction.

Graphene-collagen cryogel controls neuroinflammation and fosters accelerated axonal regeneration in spinal cord injury.

Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function. The pathology of SCI is multifaceted and involves a cascade of events, including neuroinflammation and neuronal degeneration at the epicenter, limiting repair process. We developed a supermacroporous, mechanically elastic, electro-conductive, graphene crosslinked collagen (Gr-Col) cryogels for the regeneration of the spinal cord post-injury. The effects of graphene in controlling astrocytes reactivity and microglia polarization are evaluated in spinal cord slice organotypic culture and rat spinal cord lateral hemisection model of SCI. In our work, the application of external electric stimulus results in the enhanced expression of neuronal markers in an organotypic culture. The implantation of Gr-Col cryogels in rat thoracic T9-T11 hemisection model demonstrates an improved functional recovery within 14 days post-injury (DPI), promoted myelination, and decreases the lesion volume at the injury site. Decrease in the expression of STAT3 in the implanted Gr-Col cryogels may be responsible for the decrease in astrocytes reactivity. Microglia cells within the implanted cryogels shows higher anti-inflammatory phenotype (M2) than inflammatory (M1) phenotype. The higher expression of mature axonal markers like ß-tubulin III, GAP43, doublecortin, and neurofilament 200 in the implanted Gr-Col cryogel confirms the axonal regeneration after 28 DPI. Gr-Col cryogels also modulate the production of ECM matrix, favouring the axonal regeneration. This study shows that Gr-Col cryogels decreases neuroinflammation and accelerate axonal regeneration.

Research progress on the role and regulatory mechanism of pathogenic Th17 cells in neuroinflammation.

Neuroinflammation is a complex immune response in the central nervous system against various factors such as injury, infection and toxins which interfere with homeostasis, involving a variety of immune cells lingering in the central nervous system. Persistent neuroinflammation is a common denominator of the etiology and course of all neurological diseases, including neurodevelopmental, neurodegenerative and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and depression. Th17 cells, known as an important subtpye of CD4 + T cells, mediate immune responses against extracellular bacteria and fungi in steady-state and maintain the defense function of the intestinal mucosal barrier. However, when the cytokine microenvironment in vivo undergoes inflammatory changes, Th17 cells can transform into a highly pro-inflammatory pathogenic phenotype, break through the blood-brain barrier and recruit more inflammatory cells to participate in neuroinflammation, ultimately leading to neurodegeneration. In this review, we summarize the differentiation regulation of pathogenic Th17 cells and their roles in neuroinflammation, which is informative for understanding the interactions between immune system and nervous system.

Inflammation at the crossroads of COVID-19, cognitive deficits and depression.

Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain are being actively investigated. Due to the heterogeneous manifestations of neurological outcomes, it is possible that different mechanisms operate following SARS-CoV-2 infection, which may include direct brain infection by SARS-CoV-2, mechanisms resulting from hyperinflammatory systemic disease, or a combination of both. Inflammation is a core feature of COVID-19, and both central and systemic inflammation are known to lead to acute and persistent neurological alterations in other diseases. Here, we review evidence indicating that COVID-19 is associated with neuroinflammation, along with blood-brain barrier dysfunction. Similar neuroinflammatory signatures have been associated with Alzheimer's disease and major depressive disorder. Current evidence demonstrates that patients with pre-existing cognitive and neuropsychiatric deficits show worse outcomes upon infection by SARS-CoV-2 and, conversely, COVID-19 survivors may be at increased risk of developing dementia and mood disorders. Considering the high prevalence of COVID-19 patients that recovered from infection in the world and the alarming projections for the prevalence of dementia and depression, investigation of possible molecular similarities between those diseases may shed light on mechanisms leading to long-term neurological abnormalities in COVID-19 survivors.

Targeting neuroinflammation by polyphenols: A promising therapeutic approach against inflammation-associated depression.

Depression is the most prevalent and debilitating mental disorder that affects a substantial number of people globally, hindering all aspects of their lives and leading to a high number of suicides each year. Despite the availability of an array of antidepressant medications, taking these medications does not relieve depressive symptoms in a considerable number of patients, implying that an incomplete understanding of the pathomechanisms involved in the development of depression. Besides that, a subset of those non-responsive patients exhibits an increased systemic and central inflammatory response, which has collectively led to the evolvement of the inflammatory theory of depression. Indeed, peripherally generated inflammatory mediators, as well as insults within the brain, can activate the brain's resident immune cells, resulting in a neuroinflammatory response that interferes with the multitude of neurobiological domains implicated in the pathogenesis of depression. Polyphenols, a group of plant-derived bioactive molecules, have been shown to exert neuroprotective functions on the brain by influencing an array of neuropathological mechanisms, including neuroinflammation. From these perspectives, this review mechanistically provides an overview of the neuropathological roles of sustained neuroinflammatory response in the development of depression and elucidates the therapeutic potential of flavonoid and nonflavonoid polyphenols in modulating inflammatory mediators and signaling cascades as well as promoting other neurophysiological and neuroprotective functions underlying inflammation-associated depressive symptoms. Therefore, given their significant anti-neuroinflammatory effects, polyphenols could be a promising and effective adjunctive therapy for the treatment of neuropsychiatric symptoms associated with inflammation-related depression.

IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation.

During inflammation, Ly6Chi monocytes are rapidly mobilized from the bone marrow (BM) and are recruited into inflamed tissues, where they undergo monocyte-to-phagocyte transition (MTPT). The in vivo developmental trajectories of the MTPT and the contribution of individual cytokines to this process remain unclear. Here, we used a murine model of neuroinflammation to investigate how granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-γ (IFNγ), two type 1 cytokines, controlled MTPT. Using genetic fate mapping, gene targeting and high-dimensional single-cell multiomics analyses, we found that IFNγ was essential for the gradual acquisition of a mature inflammatory phagocyte phenotype in Ly6Chi monocytes, while GM-CSF was required to license interleukin-1ß (IL-1ß) production, phagocytosis and oxidative burst. These results suggest that the proinflammatory cytokine environment guided MTPT trajectories in the inflamed central nervous system (CNS) and indicated that GM-CSF was the most prominent target for the disarming of monocyte progenies during neuroinflammation.

Omarigliptin/galangin combination mitigates lipopolysaccharide-induced neuroinflammation in rats: Involvement of glucagon-like peptide-1, toll-like receptor-4, apoptosis and Akt/GSK-3ß signaling.

AIMS: The objectives of this work were to assess the possibility of administration of omarigliptin and/or galangin to combat lipopolysaccharide (LPS)-induced neuroinflammation in rats and to explore the possible mechanisms that might contribute to their actions. MATERIALS AND METHODS: In a rat model of LPS-induced neuroinflammation, the changes in the behavioral tests, biochemical parameters, and the histopathological picture were assessed. KEY FINDINGS: Administration of either omarigliptin or galangin to LPS-injected rats was able to significantly improve the behavioral changes with restoration of the oxidant/antioxidant balance, decrement of toll-like receptor-4 levels, and amelioration of the neuroinflammation associated with inhibition of apoptosis and restoration of glucagon-like peptide-1 levels in the cerebral tissues. In addition, omarigliptin and/or galangin significantly reduced the levels of phospho-Akt and glycogen synthase kinase 3 beta (GSK-3ß) and significantly increased the expression of beclin-1 in the cerebral tissues compared versus the group treated with LPS alone. As a result, these changes were positively reflected on the histopathological and the electron microscopic picture of the cerebral tissues. These beneficial effects were maximally evidenced in rats treated with omarigliptin/galangin combination relative to the use of either omarigliptin or galangin alone. SIGNIFICANCE: Omarigliptin/galangin combination might be proposed as a promising therapeutic line for mitigation of the pathophysiologic events of LPS-induced neuroinflammation.

Nervous system consequences of COVID-19.

Neurological symptoms highlight the need to understand pathophysiologic mechanisms.

Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors.

Ischemia in the medial prefrontal cortex (mPFC) causes cognitive impairment in stroke cases. This study aimed to examine the effects of varenicline as α7 and α4ß2 nicotine acetylcholine receptors (nAChRs) agonist, on cognitive impairment, inflammation, apoptosis, and synaptic dysfunction in mPFC ischemia. Mice were divided to three groups of control, sham, or photothrombotic mPFC ischemia model. The control and sham groups received 2 ml/kg of normal saline for a 14-day period. As well, the animals in the ischemia groups received normal saline (2 ml/kg) or varenicline at 0.1, 1, and 3 mg/kg doses for a 14-day period. Anxiety-like behaviors were then assessed by open field (OFT) and elevated plus-maze (EPM) tests. Memory was also evaluated using Morris water maze (MWM) and novel object recognition (NOR) tests. The levels of inflammatory (IL-1ß, TNF-α), apoptotic (Bax, caspase3, BCL-2), and synaptic (SYP, PSD-95, and GAP-43) proteins were examined using the western blot method. In addition, the histological evaluation was performed to assess tissue damage. The administration of Varenicline at the dose of 3 mg/kg reduced the IL-1ß, TNF-α, Bax, and caspase3 levels. Moreover, it increased BCL-2, SYP, PSD-95, and GAP-43 levels at the same dose and ameliorated memory impairment and anxiety-like behaviors in mPFC ischemic mice. Varenicline improved cognitive impairment by blocking inflammation and apoptosis, improving synaptic factors, and diminishing tissue damage in the mPFC ischemic mice.

Lipopolysaccharide induced altered signaling pathways in various neurological disorders.

Neuroinflammation is defined as an inflammatory response within the brain or spinal cord, whereas the brain's innate immune system is triggered by various inflammatory challenges such as injury, infection, exposure to toxin (LPS) and ageing, which result in cognitive impairment and neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Lipopolysaccharide (LPS) is a main structural component of the outer membrane of gram-negative bacteria, widely used systematically to stimulate the immune system and to generate profound physiological and behavioural changes. It consists of three parts: lipid A, a core oligosaccharide and an O side chain. It is reported by several scientists that, besides the systemic alteration, LPS also induces neurodegeneration by promoting neuroinflammation upon binding with the stimulation of Toll-like receptor-4 (TLR4) receptors present on glial cells. The mammalian Toll-like receptor (TLR) family consists of 13 membranes and TLR was discovered as a crucial pattern recognition receptor (PPR) involved in the recognition of pathogen-associated molecular patterns (PAMPs). Future studies will show that damage/danger-associated molecular patterns (DAMPs) are recognised by the involvement of PPRs, generated by the host itself. The stimulation of TLR4 by lipopolysaccharide phosphorylates two signalling pathways, namely the MyD88-dependent pathway and the MyD88-independent pathway. This activation subsequently triggers the release of various pro-inflammatory cytokines that are necessary to activate innate immune responses, and then promotes neuroinflammation. In this review, we critically demonstrated the epidemiology of neuroinflammation, types of TLRs, the molecular mechanism of TLR4 and management of neuroinflammation.

Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease: A Case Series.

BACKGROUND AND OBJECTIVES: Despite detection of autoantibodies, anti-IgLON5 disease was historically considered a tau-associated neurodegenerative disease, with limited treatment options and detrimental consequences for the patients. Observations in increasing case numbers hint toward underlying inflammatory mechanisms that, early detection provided, open a valuable window of opportunity for therapeutic intervention. We aimed to further substantiate this view by studying the CSF of patients with anti-IgLON5. METHODS: We identified 11 patients with anti-IgLON5 from our database and compared clinical, MRI, and CSF findings with a cohort of 20 patients with progressive supranuclear palsy (PSP) (as a noninflammatory tauopathy) and 22 patients with functional neurologic disorder. RESULTS: Patients with anti-IgLON5 show inflammatory changes in routine CSF analysis, an increase in B-lymphocyte frequency, and the presence of plasma cells in comparison to the PSP-control group and functional neurologic disease controls. Patients with intrathecal plasma cells showed a clinical response to rituximab. DISCUSSION: Our findings indicate the importance of inflammatory mechanisms, in particular in early and acute anti-IgLON5 cases, which may support the use of immune-suppressive treatments in these cases. The main limitation of the study is the small number of cases due to the rarity of the disease.

Targeting neuroinflammation by intranasal delivery of nanoparticles in neurological diseases: a comprehensive review.

Neuroinflammation (NIF) plays an essential role in the pathology of neurological disorders like Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy. Despite progress in the drug discovery and development of new drugs, drug delivery to the central nervous system (CNS) still represents the challenge due to the presence of the blood-brain barrier (BBB). Targeting NIF may require an adequate amount of drug to cross the BBB. Recently, the intranasal (IN) drug administration has attracted increasing attention as a reliable method to cross the BBB and treat neurological disorders. On the other hand, using optimized nanoparticles may improve the IN delivery limitations, increase the mucoadhesive properties, and prevent drug degradation. NPs can carry and deliver drugs to the CNS by bypassing the BBB. In this review, we described briefly the NIF as a pathologic feature of CNS diseases. The potential treatment possibilities with IN transfer of NP-loaded drugs will enhance the establishment of more efficient nanoformulations and delivery systems.

Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) suffer from depression at higher rates than the general population. An etiological trigger of depressive symptoms is theorised to be inflammation within the central nervous system. It is believed that heightened intestinal inflammation and dysfunction of the enteric nervous system (ENS) contribute to impaired intestinal permeability, which facilitates the translocation of intestinal enterotoxins into the blood circulation. Consequently, these may compromise the immunological and physiological functioning of distant non-intestinal tissues such as the brain. In vivo models of colitis provide evidence of increased blood-brain barrier permeability and enhanced central nervous system (CNS) immune activity triggered by intestinal enterotoxins and blood-borne inflammatory mediators. Understanding the immunological, physiological, and structural changes associated with IBD and neuroinflammation may aid in the development of more tailored and suitable pharmaceutical treatment for IBD-associated depression.