Search

Anesthetic sevoflurane (Sev) causes cognitive dysfunction and neuronal death when used as an anesthetic during surgical procedures. Gynosaponin (GpS) was studied for its effects on brain morphology and cognitive behaviors in Sevanesthetized rats. The present study investigated whether GpS has an effect on Sev anesthesia-induced abnormalities in brain morphology and cognitive behaviors, as well as on apoptosis and inflammation of neurons in rats, and delved into the molecular mechanisms. Male Sprague-Dawley rats were induced by 3% Sev anesthesia, and GpS was injected into the rats via the tail vein. The in vitro model of Sev anesthesia was constructed by treating primary rat hippocampal neurons with 4.1% Sev in the presence of GpS (5, 10, and 20 µM). The neuroprotective effects of GpS against Sev-induced cognitive deficits in rats were evaluated using the open field and Morris water maze tests. The apoptosis of hippocampal neurons was observed using hematoxylin-eosin (HE staining and TUNEL assay. Cleaved caspase-3 expression and reactive oxygen species production in rat hippocampal tissue were measured by immunofluorescence. Apoptosis-related proteins and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were determined via Western blot. Pro-inflammatory factors tumor necrosis factor-a and interleukin-6 were measured via ELISA. Levels of malondialdehyde, superoxide dismutase and glutathione were assayed by commercial kits. Viability and apoptosis of hippocampal neurons were detected by Cell Counting Kit-8 and flow cytometry. Expression of cleaved caspase-3, B-cell leukemia/lymphoma 2 protein (Bcl-2) Bcl-2-associated protein (Bax) was determined by Western blot. GpS significantly reduced Sev-induced decline in short-term memory, learning and cognitive abilities, as well as neuronal degeneration apoptosis and inflammatory responses, GpS also lessened oxidative stress damage, and activated the PI3K/Akt/mTOR pathway (p<0.05). GpS therapy enhanced learning and memory abilities in rats suffering from Sev-induced cognitive deficits. The PI3K/Akt/mTOR pathway inhibitor LY294002 reversed the ameliorative effects of high-dose GpS on cognitive deficits and cell damage in primary hippocampal neurons in Sev anesthetized rats (p<0.05). We conclude that GpS ameliorates Sev-induced neurotoxicity and cognitive dysfunction by modulating the PI3K/Akt/mTOR pathway and alleviating neuronal apoptosis and oxidative stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model, high-sugar and high-fat dietinduced model and spontaneous animal model. Establishing a simple, easy, short-cycle, safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. OBJECTIVE: To further explore and evaluate the method of building diabetic encephalopathy rat models. METHODS: Twenty Sprague-Dawley rats were randomly divided into control (n=10) and model (n=10) groups. Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity, and those in the control group were given the same amount of citrate buffer. During the experiment, the body mass, feed intake, water intake and blood glucose were measured. After 8 weeks, the glucose tolerance and oxidative stress levels were measured, and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups. RESULTS AND CONCLUSION: Compared with the control group, the food intake, water intake, encephalization quotient, blood glucose and area under the blood glucose curve were significantly increased in the model group, while the body mass decreased significantly (P < 0.01). Histopathological examination of the brain showed that compared with the control group, the number of surviving nerve cells was significantly reduced in the model group (P < 0.01), with more significant pathological damage of nerve cells. Compared with the control group, the activities of serum superoxide dismutase, catalase and glutathione in the model group were significantly decreased (P < 0.01), and the content of oxidative malondialdehyde was significantly increased (P < 0.05). The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group, while the expression of Bcl-2 decreased (P < 0.01). In conclusion, an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats, to successfully establish the rat model of diabetic encephalopathy. [ABSTRACT FROM AUTHOR]

Background: Sevoflurane (Sev) is an inhalational anesthetic for surgical procedures where it can trigger cognitive dysfunction and neuronal apoptosis. Gyosaponin (GpS) was studied for its effects on brain morphology and cognitive behaviors in Sev-anesthetized rats., Methods: Male Sprague-Dawley rats were induced by 3 % Sev anesthesia, and 25 mg/kg and 100 mg/kg GpS were injected into the rats by tail vein. The in vitro model of Sev anesthesia was constructed by treating primary rat hippocampal neurons with 4.1 % Sev in the presence of GpS (5, 10, and 20 μM). The neuroprotective effects of GpS against Sev-induced cognitive deficits in rats were evaluated using the open field and Morris water maze tests. The apoptosis of hippocampal neurons was observed using HE staining and TUNEL assay. Apoptosis-related proteins and proteins related to the PI3K/Akt/mTOR pathway were determined via Western blot. Also, pro-inflammatory factors were measured via ELISA., Results: GpS diminished the Sev-triggered apoptosis in neurons and Cleaved caspase-3, BAX, TNF-α, IL-6, lessened oxidative stress damage, and stimulated the PI3K/Akt/mTOR pathway. GpS therapy markedly enhanced learning and memory abilities in rats suffering from Sev-related cognitive impairments., Conclusion: GpS ameliorates Sev-induced neurotoxicity and cognitive dysfunction by modulating the PI3K/Akt/mTOR pathway and alleviating neuronal apoptosis and oxidative stress., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objective: This study aimed to analyze the role of mitochondrial Omi/HtrA2 signaling pathway in neuronal apoptosis in patients with cerebral hemorrhage (CH)., Methods: In this retrospective analysis, the clinical data of 60 patients with CH who received craniotomy or minimally invasive intracranial hematoma (MIIH) were included in the case group, which was sub-divided into a craniotomy group (n=22) and a minimally invasive group (n=38) depending on the type of surgery. The brain tissue specimens of the above patients were retained in the surgical specimen repository of Yuhuan Second People's Hospital. Another 15 normal brain tissue samples retained in the surgical specimen repository were included in the normal group. The expression levels of Omi/HtrA2, X-linked inhibitor of apoptosis protein (XIAP), poly-adenosine diphosphate-ribose polymerase (PARP), pro-caspase 3, and pro-caspase 9 were determined using Western blotting., Results: The case group exhibited a higher proportion of neuronal apoptosis, higher expression levels of Omi/HtrA2, PARP, and pro-caspase 3 and 9, higher activities of caspase 3 and caspase 9 ( P < 0.05), and lower XIAP expression ( P < 0.05) in brain tissue than the normal group. The proportion of neuronal cell apoptosis in brain tissues was positively correlated with the expression of Omi/HtrA2, PARP, and pro-caspase 3 and pro-caspase 9 ( r > 0, P < 0.05), and the activity of caspase 3 and caspase 9 was negatively correlated with XIAP expression ( r < 0, P < 0.05). Compared with the craniotomy group, the minimally invasive group demonstrated higher efficacy and hematoma removal rate, shorter hematoma removal time, hematoma drainage time, operation time, and hospital stay, less intraoperative bleeding, and lower postoperative complication rates ( P < 0.05). The minimally invasive group showed higher expression level of serum XIAP and lower levels of serum caspase 3 and caspase 9 than the craniotomy group ( P < 0.05)., Conclusions: Mitochondrial Omi/HtrA2 signaling pathway may be involved in neuronal apoptosis. MIIH has the advantages of high efficacy, high hematoma clearance rate, and few complications for the treatment of CH., Competing Interests: None., (AJTR Copyright © 2023.)