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Spinal cord injury (SCI) is a common devastating condition that causes neuronal loss and dysfunction. Neuroinflammation takes cardinal roles in the pathogenesis of SCI, and nucleotide‐binding domain‐like receptor protein 3 (NLRP3) inflammasome is a mediator of inflammatory reactions occurring in SCI patients. The present study was designed to survey possible relation between thoracic segments whereby injury occurs with the activity of NLRP3 inflammasome complex, and to find the influence of hormonal therapy on the outcomes. Adult male Wistar rats underwent contusion SCI model at three different thoracic segments T1, T6 and T12, then receiving subcutaneous injection of either 10 mg/kg melatonin or 25 μg/kg 17‐β estradiol (E2) every 12 hours until 72 hours post‐SCI. Inflammasome activity was assessed before and at the end of hormonal therapy. SCI rats showed decreased locomotor activity and myelination, and increased activity of the NLRP3, apoptosis‐associated speck‐like protein (ASC) and caspase‐1 at gene and protein levels. Release of interleukins (ILs) 18 and 1β was also augmented after SCI (P < 0.0.5). Hormonal therapy was most effective for targeting mRNA activity at T6 segment. Treatment with either melatonin or E2 caused a decrease in the protein activity of NLRP3 inflammasome at all segments (P < 0.0.5), except for T6 that NLRP3 protein had no response to melatonin. IL‐1β showed decreased activity in response to hormonal therapy at all segments, whilst IL‐18 protein had no change at T1 segment. It is understood that although no alteration in the activity of NLRP3 was found for SCI at different segments, the response to hormonal therapy was influenced by segment. Significance of the study: From our results, the NLRP3 inflammasome activity is not influenced by segment, but there are differences in the effect of hormonal therapy on inflammasome activity at different segments in response to melatonin or E2. These findings also provide the beneficial effects of melatonin or E2 on inflammation caused by spinal cord injury in different thoracic segments. Finally, these data can have therapeutic importance for hormone therapy of spinal cord injury. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are key producer of reactive oxygen species in liver cells. Hepatic stellate cells (HSCs) and Kupffer cells (KCs) are the two key cells for expression of NOX in liver. KCs produce only NOX2, while HSCs produce NOX1, 2, and 4, all of which play essential roles in the process of fibrogenesis within liver. These NOX subtypes are contributed to induction of liver fibrosis by acting through multiple pathways including induction of HSC activation, proliferation, survival and migration, stimulation of hepatocyte apoptosis, enhancement of fibrogenic mediators, and mediation of an inflammatory cascade in both KCs and HSCs. Significance: KCs and HSCs are two key cells for production of NOX in liver in relation to the pathology of liver fibrosis. NOX subtypes 1, 2, and 4 are inducers of fibrogenesis in liver. NOX activation favors hepatocyte apoptosis, HSC activation, and KC‐mediated inflammatory cascade in liver, all of which are responsible for generation of liver fibrosis. [ABSTRACT FROM AUTHOR]

There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain-derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group ( P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor-α, and interleukin-6 ( P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Stroke imposes a long‐term neurological disability with limited effective treatments available for neuronal recovery. Transplantation of neural stem cells (NSCs) is reported to improve functional outcomes in the animal models of brain ischemia. However, the use of cell therapy is accompanied by adverse effects, so research is growing to use cell‐free extracts such as extracellular vesicles (EVs) for targeting brain diseases. In the current study, male Wistar albino rats (20 months old) were subjected to middle cerebral artery occlusion (MCAO). Then, EVs (30 μg) were injected at 2 hours after stroke onset via an intracerebroventricular (ICV) route. Measurements were done at day 7 post‐MCAO. EVs administration reduced lesion volume and steadily improved spontaneous locomotor activity. EVs administration also reduced microgliosis (ionized calcium‐binding adaptor molecule 1 (Iba1)+ cells) and apoptotic (terminal‐deoxynucleotidyl transferase mediated nick end labelling [TUNEL]) positive cells and increased neuronal survival (neuronal nuclear (NeuN)+ cells) in the ischemic boundary zone (IBZ). However, it had no effect on neurogenesis within the sub‐ventricular zone (SVZ) but decreased cellular migration toward the IBZ (doublecortin (DCX)+ cells). The results of this study showed neuroprotective and restorative mechanisms of NSC‐EVs administration, which may offer new avenues for therapeutic intervention of brain ischemia. Significance of the study: Based on our results, EVs administration can effectively reduce microglial density and neuronal apoptosis, thereby steadily improves functional recovery after MCAO. These findings provide the beneficial effect of NSC‐EVs as a new biological treatment for stroke. [ABSTRACT FROM AUTHOR]