Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1β/KCC2 signaling during early development

Zhang, Donghang; Yang, Yujiao; Yang, Yujie; Liu, Jin; Zhu, Tao; Huang, Han; Zhou, Cheng

doi:10.1186/s12916-022-02434-w

Cited by 9 publications

(7 citation statements)

References 60 publications

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“…The activated microglia would undergo polarization into the M1 (pro-inflammatory) phenotype, resulting in further cytokine release. Our previous study showed that neonatal LPS injection resulted in sustained production of IL-1β, but not TNF-α or IL-6, in the brain [20]. It is well known that IL-1β is critical for maintaining brain hemostasis [21].…”

Section: Introductionmentioning

confidence: 97%

Involvement of IL-1β-Mediated Necroptosis in Neurodevelopment Impairment after Neonatal Sepsis in Rats

Liao,

Zhu,

Huang

2023

IJMS

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The mechanism of long-term cognitive impairment after neonatal sepsis remains poorly understood, although long-lasting neuroinflammation has been considered the primary contributor. Necroptosis is actively involved in the inflammatory process, and in this study, we aimed to determine whether neonatal sepsis-induced long-term cognitive impairment was associated with activation of necroptosis. Rat pups on postnatal day 3 (P3) received intraperitoneal injections of lipopolysaccharide (LPS, 1 mg/kg) to induce neonatal sepsis. Intracerebroventricular injection of IL-1β-siRNA and necrostatin-1 (NEC1) were performed to block the production of IL-1β and activation of necroptosis in the brain, respectively. The Morris water maze task and fear conditioning test were performed on P28–P32 and P34–P35, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-PCR), and Western blotting were used to examine the expression levels of proinflammatory cytokines and necroptosis-associated proteins, such as receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Sustained elevation of IL-1β level was observed in the brain after initial neonatal sepsis, which would last for at least 32 days. Sustained necroptosis activation was also observed in the brain. Knockdown of IL-1β expression in the brain alleviated necroptosis and improved long-term cognitive function. Direct inhibition of necroptosis also improved neurodevelopment and cognitive performance. This research indicated that sustained activation of necroptosis via IL-1β contributed to long-term cognitive dysfunction after neonatal sepsis.

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Section: Introductionmentioning

confidence: 97%

Involvement of IL-1β-Mediated Necroptosis in Neurodevelopment Impairment after Neonatal Sepsis in Rats

Liao,

Zhu,

Huang

2023

IJMS

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“…Old age, fair skin, long-term sun exposure, long-term immunosuppression, and previous skin cancer diagnosis are all important risk factors for cSCC[ 10 ]. In addition, long-term skin inflammation seems to contribute to the development of cSCC, such as chronic wound, ulcer, sinus tract, burn, or scar[ 11 ]. This patient developed cSCC mainly due to repeated skin ulceration, leading to local chronic inflammation and popliteal squamous cell carcinoma, which not only affects the functional recovery of knee joint but also increases the probability of malignant degeneration and the difficulty of popliteal defect reconstruction.…”

Section: Discussionmentioning

confidence: 99%

Giant cutaneous squamous cell carcinoma of the popliteal fossa skin: A case report

Wang¹,

Li²,

Chao³

et al. 2022

World J Clin Cases

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BACKGROUND Cutaneous squamous cell carcinoma (cSCC) is a common malignant hyperplasia of the skin epithelium. However, cSCC progressing to giant squamous cell carcinoma of the popliteal fossa skin has not been reported. We used full-thickness skin graft from the lower left quadrant of the abdomen to reconstruct the popliteal fossa skin defect in our patient. CASE SUMMARY A 64-year-old woman presented with a 3-year history of a progressively enlarged integumentary tumor located on her left popliteal fossa, which was surgically treated. The resultant defect (15 cm × 25 cm) was repaired using full-thickness skin graft from the lower left quadrant of the abdomen. CONCLUSION Full-thickness skin graft is a good choice to repair popliteal fossa defect.

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“…The conditioned fear test can be used to examine associative learning and memory functions in rats ( Zhang et al, 2022 ). Conditioned fear experiments were performed on days 12 and 13 after sevoflurane inhalation.…”

Section: Methodsmentioning

confidence: 99%

C/EBPα involvement in microglial polarization via HDAC1/STAT3 pathway aggravated sevoflurane-induced cognitive impairment in aged rats

Wang

Yao

Zhao

et al. 2023

PeerJ

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Background Postoperative cognitive dysfunction (POCD) is a clinically frequent postoperative complication in the elderly, which is mainly manifested by the occurrence of cognitive dysfunction after anesthetized surgery in patients. To explore the involvement of C/EBPα in microglial polarization in sevoflurane anesthesia induced cognitive impairment in aged rats. Methods Sprague-Dawley (SD) rats were anesthetized by inhalation of 3% sevoflurane for 6 h to establish the POCD model. The histopathological structure of hippocampus was observed by hematoxylin and eosin (HE) staining. Associative learning and memory function and spatial learning and memory function were assessed by conditioned fear test and water maze test. The concentrations of inflammatory factors in the hippocampus were measured by ELISA. The levels of microglial activation marker (Iba1) and microglial M1 (CD86) and M2 (CD206) polarization markers were determined by immunofluorescence staining and RT-qPCR, respectively. The transcriptional regulation of HDAC1 by C/EBPα was confirmed by dual luciferase reporter assay and ChIP assay. Results Sevoflurane-induced pathomorphological damage in the hippocampal tissue of aged rats, accompanied by elevated expression of C/EBPα. Silencing of C/EBPα alleviated hippocampal histopathological injury, inhibited M1 microglial activation and the expression of M1 marker CD86, enhanced the expression of M2 marker CD206. C/EBPα transcriptionally activated HDAC1. Knockdown of C/EBPα downregulated the expression of HDAC1 and STAT3 phosphorylated proteins, which inhibited the pro-inflammatory factors (IL-6 and TNF-α) and accelerated anti-inflammatory factors (IL-10 and TGF-β) secretion. In addition, silencing of C/EBPα caused rats to have a delayed freezing time in contextual conditioned fear, a shorter escape latency, and an increased number of platform crossings. Conclusion Inhibition of C/EBPα promotes the M2 polarization of microglia and reduces the production of pro-inflammatory cytokines to alleviate the cognitive dysfunction of sevoflurane-induced elderly rats by HDAC1/STAT3 pathway.

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Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1β/KCC2 signaling during early development

Cited by 9 publications

References 60 publications

Involvement of IL-1β-Mediated Necroptosis in Neurodevelopment Impairment after Neonatal Sepsis in Rats

Involvement of IL-1β-Mediated Necroptosis in Neurodevelopment Impairment after Neonatal Sepsis in Rats

Giant cutaneous squamous cell carcinoma of the popliteal fossa skin: A case report

C/EBPα involvement in microglial polarization via HDAC1/STAT3 pathway aggravated sevoflurane-induced cognitive impairment in aged rats

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