Molecular medicine reports
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Postoperative cognitive dysfunction (POCD) is a severe complication characterized by cognitive dysfunction following anesthesia and surgery. The aim of the present study was to investigate the effects of β‑site amyloid precursor protein cleavage enzyme 1 (BACE1) gene silencing on isoflurane anesthesia‑induced POCD in immature rats via the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway. Rat models were established and then transfected with BACE1 small interfering RNA and wortmannin (an inhibitor of PI3K). ⋯ Additionally, it was determined that silencing BACE1 improved the pathological state induced by isoflurane anesthesia in immature rats, and attenuated the inflammatory response and the levels of APP and Aβ in hippocampal tissues. Furthermore, it was suggested that silencing BACE1 may have promoted the activation of the PI3K/Akt signaling pathway, thereby inhibiting the apoptosis of the hippocampal CA1 region. Taken together, these results indicated that BACE1 gene silencing may improve isoflurane anesthesia‑induced POCD in immature rats by activating the PI3K/Akt signaling pathway and inhibiting the Aβ generated by APP.
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The present study aimed to investigate the effect of combined hyperbaric oxygen (HBO) and chondroitinase ABC (ChABC) enzyme therapy in a rat model of spinal cord injury (SCI) and to explore the underlying mechanisms. A total of 48 healthy male Wistar rats were randomly divided into six groups: Sham, SCI, vehicle, HBO, ChABC enzyme and HBO + ChABC. Excluding the sham group, SCI was established in rats by a clip compression injury and rats subsequently received HBO treatment for 2 weeks with or without an intraspinal injection of 0.1 U/µl ChABC. ⋯ The combined HBO and ChABC treatment significantly inhibited SCI‑induced AQP4 expression, but ChABC alone did not. Functional recovery in the HBO + ChABC group was significantly increased compared with the HBO or ChABC groups. These results indicate that combined HBO and ChABC treatment is more effective in treating SCI than either therapy alone.
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N-acetyl cysteine (NAC) has been extensively reported to exert neuroprotective effects on the central nervous system. Oxidative stress may contribute to the underlying mechanisms causing Alzheimer's disease (AD). The effect of NAC against oxidative stress injury was investigated in a cellular model of AD in the present study and the underlying mechanisms were revealed. ⋯ Another mechanism involved in the neuroprotective action of NAC may be its ability to inhibit MAPK signal transduction following H2O2 exposure. In addition, NAC may protect cells against H2O2‑induced toxicity by attenuating increased tau phosphorylation. Thus, the protective ability of NAC is hypothesized to result from inhibition of oxidative stress and downregulation of MAPK signal transduction and tau phosphorylation.
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Breakdown of the blood brain barrier (BBB) is a secondary injury following traumatic brain injury (TBI) and can lead to the development of brain edema. However, the factors that contribute to the disruption of the BBB and increase the severity of brain edema in TBI remain to be elucidated. 20‑hydroxyeicosatetraenoic acid (20‑HETE) is a metabolite of arachidonic acid. The inhibition of 20‑HETEsynthesis by HET0016 has been suggested as a strategy to decrease brain edema. ⋯ These results suggested that 20‑HETE may aggravate BBB disruption following TBI, via enhancing the expression of MMP‑9 and tight junction proteins. Furthermore, oxidative stress and the JNK signaling pathway may be involved in BBB dysregulation. In conclusion, the results of the present demonstrated that the production of 20‑HETE was increased in cerebral tissue following traumatic injury, thus suggesting that it may contribute to the compromise of BBB integrity and the development of brain edema.
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The present study aimed to investigate the mechanism by which the Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway mediates cerebral ischemia and the efficacy of pharmaceutical intervention. The rat model of middle cerebral artery occlusion (MCAO) was established and confirmed via assessment of changes in the expression of phosphorylated (p)‑JAK2, p‑STAT3, high‑mobility group box 1 (HMGB1), and inflammatory factors using ELISA and western blot analysis. The effects of JAK2/STAT3 inhibitor and curcumin on the expression of p‑JAK2, p‑STAT3, HMGB1, and inflammatory factors after cerebral ischemia were observed with ELISA, western blotting and immunohistochemical staining. ⋯ The concentration of p‑JAK2/JAK2 and p‑STAT3/STAT3 in the brain tissue homogenate of MCAO group was significantly higher than in the sham group (P<0.05). The concentrations of TNF‑α, interleukin (IL)‑1β, IL‑6, and HMGB1 in the group treated with STAT3 inhibitor (MCAO + rapamycin), JAK2 inhibitor (MCAO + AG490), and MCAO + curcumin were significantly lower than in the MCAO group (P<0.01), as well as the relative content of p‑JAK2/JAK2 and p‑STAT3/STAT3 (P<0.05). Inhibition of the JAK2/STAT3 signaling pathway, such as curcumin can reduce the expression of HMGB1 in brain tissue after cerebral ischemia, which can significantly reduce the inflammatory response after cerebral ischemia.