The etiology underlying ischemic stroke is still elusive. Previous studies have indicated that inflammation might play a key role in the pathogenesis, which provided a novel insight into the therapeutic strategy of ischemic stroke. In this review, we summarize some drugs which regulate the activation and polarization of microglia and further alleviate neurological symptoms.
Key words:
Ischemic stroke; Microglial cell; Modulation
Objective: This study aimed to investigate the characteristics of auditory processing (AP) in preschool children with attention-deficit/hyperactivity disorder (ADHD) using the speech auditory brainstem response (speech-ABR), which provides insights into the AP of speech signals in the central auditory nervous system (CANS). Method: A total of 84 preschool children diagnosed with ADHD, aged 4–6 years, were matched with 84 typically developing (TD) children based on gender and age. All children underwent speech-ABR testing, cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition or the Wechsler Intelligence Scale for Children–Fourth Edition, and a continuous performance test. Results: Children with ADHD exhibited significantly longer latencies of speech-ABR waveforms V, A, and D compared to TD children. Multiple linear regression analysis showed that the latencies of speech-ABR waves V, A, and D were affected by the presence of ADHD, but not by the full-scale intelligence quotient. Conclusions: This study revealed that preschool children with ADHD exhibited abnormal AP of speech signals in their CANS. The findings suggest that speech-ABR can be utilized as a reliable measure to evaluate AP ability in this population, as it remains unaffected by cognitive or attentional factors. The transient response (V, A) of speech-ABR was found to be a significant predictor of ADHD in a clinical setting. Early assessment of AP abnormalities via speech-ABR is recommended in preschool-age children to develop targeted interventions for ADHD. Supplemental Material: https://doi.org/10.23641/asha.26376502
To evaluate the role of Toll-like receptor 2 (TLR2) signaling in retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR).The OIR model was established in C57BL/6J wild type (WT) mice and TLR2-/- mice. Retinal neovascularization in the OIR model was measured by counting new vascular cell nuclei above the internal limiting membrane and analyzing flat-mounted retinas perfused with fluorescein dextran and immunostained with Griffonia Simplicifolia (GS) isolectin. The expression of TLR2 and VEGF in the retina was detected by immunofluorescence. Expression of TGF- β1, b-FGF, and IL-6 mRNA in the retina was measured by quantitative real-time PCR.Compared to WT OIR mice, retinal neovascularization was attenuated in TLR2-/- OIR mice. The co-expressions of TLR2 and VEGF were remarkably and consistently increased in WT OIR mice; however, there was no expression of TLR2 and a significant decrease in VEGF expression in TLR2-/- OIR mice. These results suggest that TLR2 plays a central role in OIR model angiogenesis. Expression of TGF- β1, b-FGF, and IL-6 mRNA were reduced in the TLR2-/- OIR mice, suggesting that the inflammatory response induced by TLR2 relates to angiogenesis.TLR2 signaling in the retina is associated with neovascularization in mice. Inflammation contributes to the activation of angiogenesis and is partially mediated through the TLR2-VEGF retinal signaling pathway.
Activation of the immune system via toll-like receptors (TLRs) is implicated in atherosclerosis, microvascular complications, and angiogenesis. However, the involvement of TLRs in inflammation-associated angiogenesis in ischemic neural tissue has not been investigated. The goal of this study is to determine the role of TLR4 signaling in oxygen-induced neovascularization in retina, a neural tissue.In oxygen-induced retinopathy model, we found that retinal neovascularization was significantly attenuated in TLR4(-/-) mice. The further study revealed that the absence of TLR4 led to downregulation of proinflammatory factors in association with the attenuated activation of glia in the ischemic retina, which was also associated with reduced expression of high-mobility group box-1, an endogenous ligand for TLR4. The application of high-mobility group box-1 to the ischemic retina promoted the production of proinflammatory factors in wild-type but not TLR4(-/-) mice. High-mobility group box-1 treatment in vitro also significantly promoted the production of proinflammatory factors in retinal glial cells from wild-type mice, but much less from TLR4(-/-) mice.Our results suggest that the release of high-mobility group box-1 in ischemic neural tissue initiates TLR4-dependent responses that contribute to neovascularization. These findings represented a previously unrecognized effect of TLR4 on angiogenesis in association with the activation of glia in ischemic neural tissue.
Intracerebral hemorrhage (ICH) is a fatal acute cerebrovascular disease, with a high morbidity and mortality. Following ICH, erythrocytes release heme and several of its metabolites, thereby contributing to brain edema and secondary brain damage. Heme oxygenase is the initial and rate-limiting enzyme of heme catabolism, and the expression of heme oxygenase-1 (HO-1) is rapidly induced following acute brain injury. As HO-1 exerts it effects via various metabolites, its role during ICH remains complex. Therefore, in-depth studies regarding the role of HO-1 in secondary brain damage following ICH may provide a theoretical basis for neuroprotective function after ICH. The present review aims to summarize recent key studies regarding the effects of HO-1 following ICH, as well as its influence on ICH prognosis.
Inflammatory responses contribute to the pathogenesis of various neurological diseases, and microglia plays an important role in the process. Activated microglia can differentiate into the pro-inflammatory, tissue-damaging M1 phenotype or the anti-inflammatory, tissue-repairing M2 phenotype. Regulating microglia differentiation, hence limiting a harmful response, might help improve the prognosis of inflammation-related nervous system diseases. The present study aimed 1. to observe the anti-inflammatory effect of lipoxin A4 (LXA4) on the inflammatory response associated to lipopolysaccharide (LPS)-induced microglia activation, 2. to clarify that LXA4 modulates the activation and differentiation of microglia induced by LPS stimulation, 3. to determine whether LXA4 regulates the activation and differentiation of microglia through the Notch signaling pathway, 4. to provide a foundation for the use of LXA4 for the treatment of inflammatory related neurological diseases. To construct a model of cellular inflammation, immortalized murine BV2 microglia cells were provided 200 ng/ml LPS. To measure the mRNA and protein levels of inflammatory factors (interleukin [IL]-1β, IL-10, and tumor necrosis factor [TNF]-α) and M1 and M2 microglia markers (inducible nitric oxide synthase [iNOS], cluster of differentiation [CD]32, arginase [Arg]1, and CD206), we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), immunofluorescence, or flow cytometry. To determine the mRNA and protein levels of Notch signaling components (Notch1, Hes1, and Hes5), we performed qRT-PCR and western blot. LXA4 inhibits the expression of Notch1 and Hes1 associated with M1 type microglial differentiation and decreases the M1 type microglia marker iNOS and related inflammatory factors IL-1β and TNF-α. Moreover, LXA4 upregulates the expression of the M2-associated Hes5, as well as the expression of the M2 microglia marker Arg1 and the associated inflammatory factor IL-10. These effects are blocked by the administration of the γ-secretase inhibitor DAPT, a specific blocker of the Notch signaling pathway. LXA4 inhibits the microglia activation induced by LPS and the differentiation into M1 type with pro-inflammatory effect, while promoting the differentiation to M2 type with anti-inflammatory effect. LXA4 downregulates the inflammatory mediators IL-1β, TNF-α, and iNOS, while upregulating the anti-inflammatory mediator IL-10, which acts through the Notch signaling pathway.
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