Sepsis-associated encephalopathy (SAE) is a common manifestation of sepsis that may lead to cognitive decline. Our aim was to investigate whether the neurofilament light chain (NFL) and soluble tri...

Antigen-specific immune responses are crucially involved in both multiple sclerosis (MS) and myasthenia gravis (MG). Teriflunomide is an immunomodulatory agent approved for treatment of MS through inhibition of lymphocyte proliferation. MG associated with muscle-specific tyrosine kinase (MuSK) antibodies often manifests with a severe disease course, prompting development of effective treatment methods. To evaluate whether teriflunomide treatment may ameliorate MuSK-autoimmunity, experimental autoimmune MG (EAMG) was induced by immunizing C57BL/6 (B6) mice three times with MuSK in complete Freund’s adjuvant (CFA) (n = 17). MuSK-immunized mice were treated daily with teriflunomide (n = 8) or PBS (n = 9) starting from the third immunization (week 8) to termination (week 14). Clinical severity of EAMG was monitored. Immunological alterations were evaluated by measurement of anti-MuSK IgG, neuromuscular junction deposits, and flow cytometric analysis of lymph node cells. In MS patients under teriflunomide treatment, the peripheral blood B cell subset profile was analyzed. B6 mice treated with teriflunomide displayed relatively preserved body weight, lower EAMG prevalence, reduced average clinical grades, higher inverted screen scores, diminished anti-MuSK antibody and NMJ deposit levels. Amelioration of EAMG findings was associated with reduced memory B cell ratios in the lymph nodes. Similarly, MS patients under teriflunomide treatment showed reduced memory B cell, plasma cell, and plasmablast ratios. Teriflunomide treatment has effectively ameliorated MuSK-autoimmunity and thus may putatively be used in long-term management of MuSK-MG as an auxiliary treatment method. Teriflunomide appears to exert beneficial effects through inhibition of effector B cells.

Introduction: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination and brain pericyte dysfunction might be involved in MS pathogenesis Our aim was to evaluate whether the factors in serum affect pericyte survival. Method: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce experimental autoimmune encephalomyelitis (EAE). To confirm the animal model, the sera level of anti-MOG antibody in mice and platelet-derived growth factor-BB (PDGF-BB) in patients was measured by ELISA. Human brain vascular pericytes (HBVP) cell lines were incubated with sera of EAE mice and primer progressive MS (PPMS), seconder progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients. The viability of HBVP is measured with Annexin V-FITC/propidium iodide staining with flow cytometry. Results: Annexin V-FITC/propidium iodide staining with flow cytometry showed increased ratios of early apoptosis and decreased survival following incubation with sera of EAE and progressive MS. Levels of platelet-derived growth factor-BB were identical in serum and cerebrospinal fluids of patients with different forms of MS. Conclusion: Our results suggest that serum factors might contribute to progressive MS pathogenesis via pericyte dysfunction.

Chemokine (CXC motif) ligand 8 (CXCL8) is a pro-inflammatory chemokine binding to CXC motif receptors 1/2 (CXCR1/2). Patients with temporal lobe epilepsy (TLE) exhibit increased serum CXCL8 levels. CXC motif ligand 1 (CXCL1), a murine ortholog of CXCL8, has been implicated in seizure generation and neuronal loss. This study evaluated the antiepileptogenic and antiseizure effects of reparixin in amygdaloid kindling rat model of TLE. Reparixin was administered during the kindling period for 14 days, and seizures were induced twice daily via electrical stimulation. To assess the antiseizure effects, reparixin was administered to fully kindled animals, and stimulations were performed 24 and 48 h later. Levetiracetam, a broad-spectrum antiseizure drug, was administered intraperitoneally (i.p.) as positive control 1 h before each stimulation. Reparixin delayed secondary seizure generalization during kindling. Reparixin reduced seizure severity and after-discharge duration in fully kindled animals at 24 h from treatment initiation. CXCR1/2 and protein kinase B pathway proteins exhibited no significant changes; reparixin reduced the phospho-extracellular signal-regulated kinase (pERK)/ERK ratio in the cortex and hippocampus. CXCL1 expression was significantly decreased in the cortex. Reparixin exhibited antiepileptogenic and partial antiseizure effects by modulating the CXCL1–CXCR1/2 axis and reducing ERK signaling. Already in clinical trials on respiratory diseases, reparixin could be repurposed for epilepsy therapy.

İstanbul Üniversitesi | Tarihten Geleceğe Bilim Köprüsü - 1453

Chemokine (CXC motif) ligand 8 (CXCL8) is a pro-inflammatory chemokine binding to CXCR1/2 receptors, is elevated in the serum of patients with Temporal Lobe Epilepsy (TLE). Its murine ortholog CXCL1, is implicated in seizure generation and neuronal loss. This study evaluates the anti-epileptogenic and anti-seizure effect of reparixin, an allosteric CXCR1/2 antagonist in amygdaloid kindling rat model of TLE. Reparixin was administered via osmotic pumps (8mg/kg/h) during kindling period over 14 days and seizures induced twice daily by electrical stimulation. To asses anti-seizure effects, fully kindled animals reparixin was given before stimulations at 24 and 48 hours post-implantation. Brain tissue was analyzed for CXCL1-CXCR1/2 axis activation. Reparixin delayed secondary seizure generalization during kindling.. While it did not completely prevent kindling, reparixin reduced seizure severity and after-discharge duration in fully kindled animals at 24 hours post-treatment. CXCR1/2 and AKT pathway proteins showed no significant changes, reparixin reduced the phospho-ERK:ERK ratio in the cortex and hippocampus. CXCL1 expression was also significantly decreased in the cortex. Reparixin exhibits anti-epileptogenic and partial anti-seizure effects by modulating the CXCL1-CXCR1/2 axis and reducing ERKsignalling, underscoring its potential as a neuroinflammation-targeting epilepsy treatment. Already in clinical trials for respiratory diseases, reparixin could be repurposed for epilepsy therapy.