98%
921
2 minutes
20
Background: Postoperative cognitive dysfunction (POCD) is characterized by impaired learning and memory. 6 h duration isoflurane anesthesia is an important factor to induce POCD, and the dysfunction of ryanodine receptor (RyR) in the hippocampus may be involved in this process. We investigated the expression of RyR3 in the hippocampus of mice after 6-h duration isoflurane anesthesia, as well as the improvement of RyR receptor agonist caffeine on POCD mice, while attempting to identify the underlying molecular mechanism.
Materials: We constructed a POCD model using 8-week-old male C57BL/6J mice that were exposed to 6-h duration isoflurane. Prior to the three-day cognitive behavioral experiment, RyR agonist caffeine were injected. Fear conditioning and location memory tests were used in behavioral studies. We also exposed the mouse neuroblastoma cell line Neuro-2a (N2A) to 6-h duration isoflurane exposure to simulate the conditions of in vivo cognitive dysfunction. We administered ryanodine receptor agonist (caffeine) and inhibitor (ryanodine) to N2a cells. Following that, we performed a series of bioinformatics analysis to discover proteins that are involved in the development of cognitive dysfunction. Rt-PCR and Western blot were used to assess mRNA level and protein expression.
Results: 6-h duration isoflurane anesthesia induced cognitive dysfunction and increased RyR3 mRNA levels in hippocampus. The mRNA levels of RyR3 in cultured N2a cells after anesthesia were comparable to those in vivo, and the RyR agonist caffeine corrected the expression of some cognitive-related phenotypic proteins that were disturbed after anesthesia. Intraperitoneal injection of RyR agonist caffeine can improve cognitive function after isoflurane anesthesia in mice, and bioinformatics analyses suggest that CaMKⅣ may be involved in the molecular mechanism.
Conclusion: Ryanodine receptor agonist caffeine may improve cognitive dysfunction in mice after isoflurane anesthesia.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.brainresbull.2023.110790 | DOI Listing |
J Integr Neurosci
August 2025
Key Laboratory of Modern Toxicology of Ministry of Education; School of Basic Medical Sciences, Nanjing Medical University, 211166 Nanjing, Jiangsu, China.
Cognitive impairment represents a progressive neurodegenerative condition with severity ranging from mild cognitive impairment (MCI) to dementia and exerts significant burdens on both individuals and healthcare systems. Vascular cognitive impairment (VCI) represents a heterogeneous clinical continuum, spanning a spectrum from subcortical ischemic VCI (featuring small vessel disease, white matter lesions, and lacunar infarcts) to mixed dementia, where vascular and Alzheimer's-type pathologies coexist. While traditionally linked to macro- and microvascular dysfunction, the mechanisms underlying VCI remain complex.
View Article and Find Full Text PDFJ Integr Neurosci
August 2025
Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 100853 Beijing, China.
Neurocognitive disorders represent a significant global health challenge and are characterized by progressive cognitive decline across conditions including Alzheimer's disease, mild cognitive impairment, and diabetes-related cognitive impairment. The hippocampus is essential for learning and memory and requires intact neuroplasticity to maintain cognitive function. Recent evidence has identified the brain insulin signaling pathway as a key regulator of hippocampal neuroplasticity through multiple cellular processes including synaptic plasticity, neurotransmitter regulation, and neuronal survival.
View Article and Find Full Text PDFTransl Neurosci
January 2025
Department of Anesthesia, The Second Affiliated Hospital of Xi'an JiaoTong University, 157 Xi Wu Road, Xi'an, 710004, Shaanxi, China.
Background: As a non-competitive blocker of the -methyl-d-aspartate receptor, ketamine is widely used for anesthesia and pain relief in clinical settings. However, certain neurological side effects may appear if it is used for the long term. According to clinical observations, anesthetic doses of ketamine trigger postoperative neurocognitive dysfunction in elderly patients, while subanesthetic doses of ketamine suppress the postoperative neuronal pyroptosis in the hippocampus, ameliorating the cognitive function.
View Article and Find Full Text PDFMagn Reson Lett
May 2025
Department of Medical Imaging, Tianjin First Central Hospital, Tianjin, 300192, China.
Hepatic encephalopathy (HE) is a neurological condition that occurs as a complication of liver dysfunction that involves sensorimotor symptoms in addition to cognitive and behavioral changes, particularly in cases of severe liver disease or cirrhosis. Previous studies have reported spatially distributed structural and functional abnormalities related to HE, but the exact relationship between the structural and functional alterations with respect to disease progression remains unclear. In this study, we performed surface-based cortical thickness comparisons and functional connectivity (FC) analyses between three cross-sectional groups: healthy controls (HC, = 51), patients with minimal hepatic encephalopathy (MHE, = 50), patients with overt hepatic encephalopathy (OHE, = 51).
View Article and Find Full Text PDFCureus
August 2025
Medical Education, Western Atlantic University School of Medicine, Freeport, BHS.
Mild cognitive impairment progresses slowly and may be reversible, providing a window of opportunity for intervention before it progresses to Alzheimer's disease, at which point treatments, at best, ameliorate symptoms with little efficacy towards delaying disease progression. The gut and brain communicate through the gut-brain axis, and derangement of the gut microbiome has been shown to promote neuroinflammation, a process intricately linked to pathological progression to mild cognitive impairment and subsequent neurocognitive diseases. In preclinical trials, probiotics modulated the gut microbiome in a way that was neuroprotective.
View Article and Find Full Text PDF