Impact of peripheral immune cells in experimental neonatal hypoxia-ischemia: A systematic review and meta-analysis.

Infiltration of peripheral immune cells into the brain following neonatal hypoxia-ischemia (HI) contributes to increased neuroinflammation and brain injury. However, the specific roles of different immune cell types in neonatal brain injury remain poorly understood. Although existing evidence suggests a potential role for sexual dimorphism in HI outcomes, this aspect has been insufficiently investigated.

Lactate administration causes long-term neuroprotective effects following neonatal hypoxia-ischemia.

Neonatal hypoxia-ischemia (HI) is one of the main causes of mortality and long-term disabilities in newborns, and the only clinical approach to treat this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models of HI. Lactate is a preferential metabolic substrate of the neonatal brain and has already been shown to produce beneficial neuroprotective outcomes in neonatal animals exposed to HI.

Lactate Protects Microglia and Neurons from Oxygen-Glucose Deprivation/Reoxygenation.

Lactate has received attention as a potential therapeutic intervention for brain diseases, particularly those including energy deficit, exacerbated inflammation, and disrupted redox status, such as cerebral ischemia. However, lactate roles in metabolic or signaling pathways in neural cells remain elusive in the hypoxic and ischemic contexts. Here, we tested the effects of lactate on the survival of a microglial (BV-2) and a neuronal (SH-SY5Y) cell lines during oxygen and glucose deprivation (OGD) or OGD followed by reoxygenation (OGD/R).

Therapeutic Hypothermia Is Limited in Preventing Developmental Impairments after Neonatal Hypoxia-Ischemia.

The only current treatment for neonatal hypoxia-ischemia (HI) is therapeutic hypothermia (TH), which still shows some limitations. Specific effects of TH in the several processes involved in brain injury progression remain unclear. In this study, the effects of TH treatment on developmental parameters, behavioral outcomes, and peripheral leukocytes were evaluated in neonatal male and female rats.

Sodium Butyrate Protects Against Intestinal Oxidative Damage and Neuroinflammation in the Prefrontal Cortex of Ulcerative Colitis Mice Model.

Inflammatory bowel diseases (IBD) cause increased inflammatory signalling and oxidative damage. IBDs are correlated with an increased incidence of brain-related disorders suggesting that the gut-brain-axis exerts a pivotal role in IBD. Butyrate is one of the main microbial metabolites in the colon, and it can cross the blood-brain barrier, directly affecting the brain.

Disruption of Bioenergetics in the Intestine of Wistar Rats Caused by Hydrogen Sulfide and Thiosulfate: A Potential Mechanism of Chronic Hemorrhagic Diarrhea in Ethylmalonic Encephalopathy.

Ethylmalonic encephalopathy (EE) is a severe inherited metabolic disorder that causes tissue accumulation of hydrogen sulfide (sulfide) and thiosulfate in patients. Although symptoms are predominantly neurological, chronic hemorrhagic diarrhea associated with intestinal mucosa abnormalities is also commonly observed. Considering that the pathophysiology of intestinal alterations in EE is virtually unknown and that sulfide and thiosulfate are highly reactive molecules, the effects of these metabolites were investigated on bioenergetic production and transfer in the intestine of rats.

Mesenchymal stromal cell-derived membrane particles: A novel cell-free therapy for inflammatory bowel diseases.

Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic and idiopathic inflammations of the gastrointestinal tract. A disruption of the epithelial barrier and an imbalance between Th1 and Th2 subsets are associated with the onset and progression of these diseases. Mesenchymal stromal cells (MSC) are a promising therapy for IBD.

Short-term effects of therapeutic hypothermia following hypoxia-ischemia in neonatal male and female rats.

Nowadays, the only treatment for human babies suffering from hypoxia-ischemia (HI) is therapeutic hypothermia (TH). However, a better understanding of the specific effects of TH in males and females is important to improve its clinical application. The present study evaluated the short-term effects of TH on the brain injury and behavioral outcomes in male and female neonatal rats submitted to neonatal HI.

Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation, fibroblast-like synoviocytes (FLS) activation and joint destruction. Fasciola hepatica is a platyhelminth that releases excretory-secretory immunomodulatory products capable of suppressing the Th1 immune response. Despite the effectiveness of available treatments for inducing disease remission, current options are not successful in all patients and may cause side effects.

Effects of living and metabolically inactive mesenchymal stromal cells and their derivatives on monocytes and macrophages.

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cells that have great potential as cell therapy for autoimmune and inflammatory disorders, as well as for other clinical conditions, due to their immunoregulatory and regenerative properties. MSCs modulate the inflammatory milieu by releasing soluble factors and acting through cell-to-cell mechanisms. MSCs switch the classical inflammatory status of monocytes and macrophages towards a non-classical and anti-inflammatory phenotype.

Lactate Administration Reduces Brain Injury and Ameliorates Behavioral Outcomes Following Neonatal Hypoxia-Ischemia.

Neonatal hypoxic-ischemic encephalopathy is a major cause of mortality and disability in newborns and the only standard approach for treating this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models. The present study evaluated the administration of lactate, a potential energy substrate of the central nervous system (CNS) in an animal model of hypoxia-ischemia (HI), that mimics in neonatal rats the brain damage observed in human newborns.

Cell membrane and bioactive factors derived from mesenchymal stromal cells: Cell-free based therapy for inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn's disease. Although the underlying mechanisms of IBD remain unclear, growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation. However, conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them.

Therapeutic ultrasound attenuates DSS-induced colitis through the cholinergic anti-inflammatory pathway.

Background: Ulcerative Colitis (UC) is an Inflammatory Bowel Disease (IBD) characterized by uncontrolled immune response, diarrhoea, weight loss and bloody stools, where sustained remission is not currently achievable. Dextran Sulphate Sodium (DSS)-induced colitis is an animal model that closely mimics human UC. Ultrasound (US) has been shown to prevent experimental acute kidney injury through vagus nerve (VN) stimulation and activation of the cholinergic anti-inflammatory pathway (CAIP).

Bioactive factors secreted from mesenchymal stromal cells protect the intestines from experimental colitis in a three-dimensional culture.

Background Aims: Although mesenchymal stromal cells (MSCs) have shown therapeutic potential in intestinal tissue repair, controversy concerning their short survival and poor biodistribution in recipient tissues still remains. Therefore, we investigated the paracrine role of MSC in three-dimensional culture of colon with experimental colitis.

Methods: Colitis was induced in mice by oral administration of dextran sulfate sodium (DSS) for 7 days.

Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis.

Aim: To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis.

Methods: Acute colitis was induced in C57Bl/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8.

Transcranial direct-current stimulation reduces nociceptive behaviour in an orofacial pain model.

Background: Transcranial direct-current stimulation (tDCS) is a noninvasive method of brain stimulation suggested as a therapeutic tool for pain and is related to the reversal of maladaptive plasticity associated with chronic pain.

Objectives: This study investigated the effect of tDCS, a non-pharmacological therapy, on local mechanical hyperalgesia, and remote thermal hyperalgesia in rats submitted to orofacial inflammatory pain model, by facial von Frey and hot plate tests, respectively. In addition, we evaluated levels of BDNF, NGF, IL-10 and IL-6 in the brainstem and blood serum of these animals at 24 hours and 7 days after the end of tDCS treatment.

Repeated systemic administration of adipose tissue-derived mesenchymal stem cells prevents tracheal obliteration in a murine model of bronchiolitis obliterans.

Objective: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ASC) administered either systemically or locally in a murine model of bronchiolitis obliterans.

Results: When compared to controls, systemic treatment with 10 ASCs on D0 and a second dose on D7 significantly prevented tracheal obliteration 28 days after heterotopic tracheal transplantation (median of 94 vs. 16%; P < 0.

Comparison of human mesenchymal stromal cells from four neonatal tissues: Amniotic membrane, chorionic membrane, placental decidua and umbilical cord.

Background: Mesenchymal stromal cells (MSCs) are being investigated as a potential alternative for cellular therapy. This study was designed to compare the biological characteristics of MSCs isolated from amniotic membrane (A-MSCs), chorionic membrane (C-MSCs), placental decidua (D-MSCs) and umbilical cord (UC-MSCs) to ascertain whether any one of these sources is superior to the others for cellular therapy purposes.

Methods: MSCs were isolated from amniotic membrane, chorionic membrane, umbilical cord and placental decidua.

Antioxidant properties of mesenchymal stem cells against oxidative stress in a murine model of colitis.

Objective: To investigate the effects of oxidative stress injury in dextran sulfate sodium (DSS)-induced colitis in mice treated with mesenchymal stem cells (MSC).

Results: Mice exposed to oral administration of 2% DSS over 7 days presented a high disease activity index and an intense colonic inflammation. Systemic infusion of MSC protected from severe colitis, reducing weight loss and diarrhea while lowering the infiltration of inflammatory cells.

Dexamethasone and azathioprine promote cytoskeletal changes and affect mesenchymal stem cell migratory behavior.

Glucocorticoids and immunosuppressive drugs are commonly used to treat inflammatory disorders, such as inflammatory bowel disease (IBD), and despite a few improvements, the remission of IBD is still difficult to maintain. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have emerged as regulators of the immune response, and their viability and activation of their migratory properties are essential for successful cell therapy. However, little is known about the effects of immunosuppressant drugs used in IBD treatment on MSC behavior.

Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis?

Aim: To investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis.

Methods: MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers.

Cell therapy for chemically induced ovarian failure in mice.

Cell therapy has been linked to an unexplained return of ovarian function and fertility in some cancer survivors. Studies modeling this in mice have shown that cells transplantation generates donor-derived oocytes in chemotherapy-treated recipients. This study was conducted to further clarify the impact of cell transplantation from different sources on female reproductive function after chemotherapy using a preclinical mouse model.