Showing papers by "Vicente Felipo published in 2023"
TL;DR: In this paper , post-mortem hippocampus was obtained from 6 controls, 19 patients with steatohepatitis (SH) and 4 patients with liver cirrhosis, depending on severity.
Abstract: BACKGROUND
Neuroinflammation in cerebral cortex of patients died with liver cirrhosis and neuroinflammation and neuronal death in cerebellum of patients died with steatohepatitis or cirrhosis, were reported. Hippocampal neuroinflammation could contribute to cognitive decline in patients with liver disease, but this has yet to be studied.The aims were to assess if hippocampus from patients died with steatohepatitis or cirrhosis show: 1) glial activation; 2) altered cytokine content; 3) immune cells infiltration; 4) neuronal apoptosis and 5) neuronal loss.
METHODS
Post-mortem hippocampus was obtained from 6 controls, 19 patients with steatohepatitis (SH) and 4 patients with liver cirrhosis. SH patients were divided in SH1 (n=9), SH2 (n=6) and SH3 (n=4) depending on severity. Glial activation, IL-1β and TNFα content, CD4 lymphocytes and monocytes infiltration, neuronal apoptosis and neuronal loss were analysed by immunohistochemistry.
RESULTS
Patients died in SH1 show astrocytes activation, whereas those died in SH2 show also microglial activation, CD4 lymphocytes and monocytes infiltration, neuronal apoptosis and neuronal loss. These changes remain in patients in SH3, who also show increased IL-1β and TNFα. Patients died in liver cirrhosis do not show CD4 lymphocytes infiltration, neuronal apoptosis or TNFα increase, but still show glial activation, increased IL-1β and neuronal loss.
CONCLUSIONS
Patients with steatohepatitis show glial activation, immune cells infiltration, apoptosis and neuronal loss. Glial activation and neuronal loss remain in cirrhotic patients. This may explain the irreversibility of some cognitive alterations in hepatic encephalopathy. Cognitive reserve may contribute to different grades of cognitive impairment in spite of similar neuronal loss.
TL;DR: Extracellular vesicles play an important role in intercellular communication and in the modulation of the immune system and neuroinflammation as mentioned in this paper , and they contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuro inflammation, including cancer, diabetes, hyperammonemia and hepatic encephalopathy.
TL;DR: In this article , the authors analyzed the cytokines released from CD4+ cell cultures and the mRNA expression of transcription factors and receptors in peripheral blood mononuclear cells to identify specific alterations of the immune system associated with the appearance of neurological alterations in MCI patients with NAFLD that could be the basis to improve and restore cognitive functions and quality of life in these patients.
Abstract: Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The mechanisms involved remain unclear. The plasma concentrations of several cytokines and chemokines were measured in 71 NAFLD patients (20 with and 51 without MCI) and 61 controls. Characterization and activation of leukocyte populations and CD4+ sub-populations were carried out and analyzed by flow cytometry. We analyzed the cytokines released from CD4+ cell cultures and the mRNA expression of transcription factors and receptors in peripheral blood mononuclear cells. The appearance of MCI in NAFLD patients was associated with increased activation of CD4+ T lymphocytes, mainly of the Th17 subtype, increased plasma levels of pro-inflammatory and anti-inflammatory cytokines such as IL-17A, IL-23, IL-21, IL-22, IL-6, INF-γ, and IL-13, and higher expression of the CCR2 receptor. Constitutive expression of IL-17 was found in cultures of CD4+ cells from MCI patients, reflecting Th17 activation. High IL-13 plasma levels were predictive of MCI and could reflect a compensatory anti-inflammatory response to the increased expression of pro-inflammatory cytokines. This study identified some specific alterations of the immune system associated with the appearance of neurological alterations in MCI patients with NAFLD that could be the basis to improve and restore cognitive functions and quality of life in these patients.