Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats

Zhang, Qi; Li, Yanan; Bao, Yongjuan; Yin, Chunyue; Xin, Xi; Guo, Yangyang; Gao, Fang; Huo, Shuping; Wang, Xiuli; Wang, Qiujun

doi:10.1186/s12871-018-0501-0

Cited by 29 publications

(23 citation statements)

References 26 publications

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“…In concur with other recent works which presented evidences of histone deacetylase-2 as player in stress-induced cognitive impairment via histone deacetylation and PI3K/AKT pathway modulation ( Verma et al, 2017 ; Wu et al, 2017 ), our results are consent with these published studies. However, the recognized biological processes leading to the pathogenesis of POCD, such as inflammation, stress, and apoptosis ( Tian et al, 2015 ; Johansson et al, 2017 ; Zhang et al, 2018 ), are less prominent in our results. Sirtuin1 (SIRT1) is a deacetylase protein that reported to mediate hippocampal neuronal apoptosis in mice and causing cognitive deficit ( Min et al, 2018 ).…”

Section: Discussioncontrasting

confidence: 80%

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

et al. 2018

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Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.

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Section: Discussioncontrasting

confidence: 80%

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

et al. 2018

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“…They demonstrated, via a rat intracranial facial nerve crush model and a nimodipine pretreatment three days prior to surgery, that nimodipine accelerates the time of functional nerve recovery [24]. Furthermore, nimodipine pretreatment reduces the incidence of postoperative cognitive dysfunction by decreasing hippocampal apoptosis in rats [25]. These data indicate that the pretreatment or prophylactic administration of nimodipine is required for its neuroprotective effect.…”

Section: Discussionmentioning

confidence: 99%

Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB

Leisz

Simmermacher

Prell

et al. 2019

IJMS

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Clinical and experimental data assumed a neuroprotective effect of the calcium channel blocker nimodipine. However, it has not been proven which neuronal or glial cell types are affected by nimodipine and which mechanisms underlie these neuroprotective effects. Therefore, the aim of this study was to investigate the influence of nimodipine treatment on the in vitro neurotoxicity of different cell types in various stress models and to identify the associated molecular mechanisms. Therefore, cell lines from Schwann cells, neuronal cells and astrocytes were pretreated for 24 h with nimodipine and incubated under stress conditions such as osmotic, oxidative and heat stress. The cytotoxicity was measured via the lactate dehydrogenase (LDH) activity of cell culture supernatant. As a result, the nimodipine treatment led to a statistically significantly reduced cytotoxicity in Schwann cells and neurons during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (p ≤ 0.05), when compared to the vehicle. The cytotoxicity of astrocytes was nimodipine-dependently reduced during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (not significant). Moreover, a decreased caspase activity as well as an increased proteinkinase B (AKT) and cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation could be observed after the nimodipine treatment under different stress conditions. These results demonstrate a cell type-independent neuroprotective effect of the prophylactic nimodipine treatment, which is associated with the prevention of stress-dependent apoptosis through the activation of CREB and AKT signaling pathways and the reduction of caspase 3 activity.

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“…A summary of the potential role of calcium dysregulation downstream of anesthetic exposure has also previously been published [117]. In vivo preclinical evidence suggesting that calcium dysregulation participates in anesthesia-mediated neurotoxicity includes the finding that nimodipine, an L-type calcium channel antagonist, protects against sevoflurane or isoflurane-induced cognitive deficits, neuroinflammation, and apoptosis [103, 118, 119]. Inhibition of the NMDA receptor with memantine has also been shown to protect against the isoflurane-mediated increase in cytosolic calcium, caspase-3 activation and cytotoxicity in vitro [120].…”

Section: Main Bodymentioning

confidence: 99%

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

2019

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Background: The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenges with cooperation during assessment and non-general anesthesia techniques, and the possibility that pre-existing cognitive impairment may impart a susceptibility to further cognitive dysfunction. Main body: This review highlights landmark and recent studies in the field, and explores potential mechanisms involved in perioperative cognitive disorders (also known as postoperative cognitive dysfunction, POCD). Specifically, we will review clinical and preclinical evidence which implicates alterations to tau protein, inflammation, calcium dysregulation, and mitochondrial dysfunction. As our population ages and the prevalence of Alzheimer's disease and other forms of dementia continues to increase, we require a greater understanding of potential modifiable factors that impact perioperative cognitive impairment. Conclusions: Future research should aim to further characterize the associated risk factors and determine whether certain anesthetic approaches or other interventions may lower the potential risk which may be conferred by anesthesia and/or surgery in susceptible individuals.

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Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats

Cited by 29 publications

References 26 publications

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction

Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

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