Inflammatory responses are associated with blood-brain barrier (BBB) dysfunction and neurological deficits following traumatic brain injury (TBI). The aim of the present study was to investigate the effects of progesterone on the expression of the inflammatory mediators prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α) in the brain, BBB permeability, cerebral edema and neurological outcome, as well as to explore the mechanism of its neuroprotective effect. In this study, male rats were randomly divided into three groups: a sham-operated group (SHAM), a TBI group (TBI) and a progesterone treatment group (TBI-PROG). The TBI model was established using a modified Feeney’s weight-dropping method. Brain samples were extracted 24 h following injury. The expression levels of COX-2 and NF-κB were examined using immunohistochemistry, whilst the expression levels of PGE2 and TNF-α were detected by enzyme-linked immunosorbent assay. BBB permeability was analyzed using Evans blue and cerebral edema was determined using the dry-wet method. The neurological outcome was evaluated using the modified neurological severity score test. The results revealed that progesterone treatment significantly reduced post-injury inflammatory response, brain edema and Evans blue dye extravasation, and improved neurological scores compared with those in the TBI group. In conclusion, the inhibition of inflammation may be an important mechanism by which progesterone protects the BBB and improves neurological outcome.
Type 2 diabetes mellitus (T2DM) markedly impairs human health. During T2DM development, some patients experience cognitive dysfunction and behavioral deficits, which are characterized by neuronal injury and memory loss. It has been reported that the incidence of dementia in middle-aged and elderly patients with diabetes is significantly higher than that in normal elderly patients. Currently, the pathogenesis of cognitive dysfunction in diabetes remains unknown, and there is no standard or specific method to diagnose the disease in clinical practice. Evidence has shown that fish oil (FO) can alleviate depressive-like behaviors by attenuating neuroinflammation in a rat model, and improve cognitive dysfunction by inhibiting apoptosis. Therefore, it is reasonable to speculate that FO may reduce cognitive impairment by attenuating neuroinflammation in diabetic rats. In the present study, we investigated the effects of FO supplementation on cognitive dysfunction in a streptozotocin-induced diabetic rat model. FO administration for 10 weeks improved spatial learning and memory as evaluated by performance in the Morris water maze (MWM). Besides, FO significantly improved the morphology of neurons in the hippocampus and cortex of diabetic rats and reduced the neuronal nuclear condensation. Moreover, FO decreased the mRNA expression of IL-1β, IL -6, and TNF-α and increased the mRNA expression of IL-4 and IL-10 in the cortex and hippocampus. FO also attenuated the brain inflammatory cascade and simultaneously reduced diabetes-induced oxidative stress. In addition, FO increased the protein expression of Nrf2 and HO-1 in cortex and hippocampus of diabetic rats. These results provide a novel horizon for the study of neuroprotective effect of FO and further clarify the connections among inflammation, oxidative stress and diabetes-induced cognitive impairment.
Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.
Airway epithelial cells, which are the first physical defense barrier against allergens, play a pivotal role in immunity, airway inflammation and airway remodeling. The damage and dysfunction of these cells trigger the development of airway inflammatory diseases. Exosomes, which exist in various bodily fluids, mediate cell-cell communication and participate in the immune response process. The present study aimed to investigate whether serum exosomes play a pro-inflammatory role in bronchial epithelial cells (BEAS-2B cells) and, if so, explore the underlying molecular mechanisms. A guinea pig model of House dust mite (HDM)-induced asthma was established by sensitizing the rodents with HdM and PBS, and serum-derived exosomes were harvested. It was found that serum-derived exosomes from HDM-sensitized guinea pigs displayed higher levels of exosomal markers than those from controls. Additionally, western blot analysis and reverse transcription-quantitative PCR indicated that serum-derived exosomes from HDM-sensitized guinea pigs carried heat shock protein 70 and triggered an inflammatory response in BEAS-2B cells via the toll-like receptor 4 (TLR4)-NF-κB pathway. However, TAK-242, an inhibitor of the expression of TLR4, blocked the activation of the TLR4-NF-κB pathway. These findings provided a novel mechanism for exosome-mediated inflammatory responses and a new perspective for the intervention of inflammatory airway disorders.
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