The Toxic Effects of S(+)-Ketamine on Differentiating Neurons In Vitro as a Consequence of Suppressed Neuronal Ca2+ Oscillations

Sinner, Barbara; Friedrich, Oliver; Zink, Wolfgang; Zausig, York; Graf, Bernhard M.

doi:10.1213/ane.0b013e31822747df

Cited by 51 publications

(58 citation statements)

References 30 publications

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“…Hippocampal neurons were prepared as described previously (Sinner et al, 2011a). Briefly, hippocampi from 19-day-old embryonic Wistar rats were prepared in ice-cold phosphatebalanced solution containing 0.05% gentamycin.…”

Section: Hippocampal Cell Culturesmentioning

confidence: 99%

“…Recent studies on neurotoxicity of ketamine show that ketamine-a non-competitive N-methyl-Daspartat (NMDA) receptor antagonist-and its stereoisomer S (+)-ketamine can trigger apoptosis (Fredriksson et al, 2004;Scallet et al, 2004;Wang et al, 2006;Slikker et al, 2007;Viberg et al, 2008;Sinner et al, 2011a;Paule et al, 2011;Brambrink et al, 2012;Liu et al, 2013). NMDA receptors are widely distributed throughout the brain and play an important role in neuronal development and differentiation (Jantzie et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Up-regulation of the NMDA receptor results in an aggravated response to normal glutamate levels resulting in excessive Ca 2+ entry and consecutively, apoptosis. Anesthetics not only induce apoptosis in the developing brain but also affect neuronal development (Vutskits et al, 2006;De Roo et al, 2009;Tan et al, 2009;Sinner et al, 2011a).…”

Section: Introductionmentioning

confidence: 99%

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Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons

et al. 2015

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Section: Hippocampal Cell Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons

et al. 2015

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“…12 Therefore, it is very likely that the mode of action of ketamine involves pancreatic islet cells, and prolonged use of ketamine may cause functional and morphological alterations of the pancreatic tissue, similar to other tissues (heart and neurons) studied previously. 18,19 Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Pancreatitis affects both the systemic and pancreatic vasculature.…”

Section: Discussionmentioning

confidence: 99%

“…By acting via the N-methyl-d-aspartate receptor, ketamine exerts its toxic effect through the suppression of neuronal Ca 2+ oscillations, down-regulation of the Ca 2+ /calmodulin kinase II, and consecutively reduces synaptic integrity. 19 EM is an accepted method to depict the histopathological changes in the pancreatic tissue. The immunohistochemical staining of pancreatic acinar cells provides understanding of exocrine functions of those cells.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Long Term Ketamine Use on Pancreatic Islet Cells

Bostan¹,

Tomak²,

Ünal³

et al. 2013

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Ketamine is a frequently used anesthetic with a prominent effect on blood glucose levels. Therefore, ketamine may alter the mode of action of pancreatic islet cells, and the prolonged use of this agent may cause functional or morphological alterations of the pancreatic tissue. This study compared prolonged and different doses of intraperitoneal ketamine administration on pancreatic islet cell morphology and secretory function in rats. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : A total of 30 rats in five groups were used. Rats in groups K40, K60, K80 and K100 received 40, 60, 80, and 100 mg/kg ketamine hydrochloride intraperitoneally (i.p.), respectively. Control group received 0.9% NaCl i.p.. Injections were repeated twice daily for 2 weeks. After 2 weeks, the animals were sacrificed under anesthesia, pancreas tissues were removed and examined using immunohistological staining, light microscopy, and electron microscopy. R Re es su ul lt ts s: : Prolonged use of ketamine caused histological alterations as observed by electron microscopy in all groups and by light microscopy in all groups except K40. Immunopositivities for insulin and glucagon was statistically significantly higher in the control group compared to study groups, but did not differ between study groups. C Co on nc cl lu us si io on ns s: : We demonstrated that the long-term ketamine use had pathological effects on the pancreas histology. Therefore, it should be kept in mind that ketamine causes pancreas damage and should be used cautiously. Further investigations are needed to find out whether these effects are permanent or not.K Ke ey y W Wo or rd ds s: : Pancreas; microscopy, electron; ketamine; immunohistochemistry Ö ÖZ ZE ET T A Am ma aç ç: : Ketamin sık kullanılan bir anestezik olup, kan glikoz düzeyi üzerinde belirgin etkisi vardır. Uzun süreli ketamin kullanımında pankreas adacık hücre morfolojisi ve salgı fonksiyonu değiştirebilir. Bu çalışmada, ratlarda farklı dozlarda ve uzun süreli ketaminin intraperitoneal (i.p.) kullanımının pankreas adacık hücre morfolojisi ve salgı fonksiyonu üzerine etkisi karşılaştırıldı. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Beş grupta 30 adet rat kullanıldı. Gruplar K40, K60, K80 ve K100 olarak dü-zenlendi ve ratlara sırasıyla 40, 60, 80 ve 100 mg/kg ketamin hidroklorür i.p. olarak verildi. Kontrol grubuna ise %0,9 NaCl i.p. uygulandı. Enjeksiyonlar 2 hafta süreyle ve günde iki kez tekrarlandı. Ratlar iki hafta sonra anestezi altında sakrifiye edilerek, pankreas dokuları çıkartıldı. Elde edilen dokular, ışık mikroskobu, elektron mikroskobu ve immünohistolojik boyama yöntemleri kullanılarak incelendi. B Bu ul lg gu ul la ar r: : Tüm uygulama gruplarında elektron mikroskobu ile histolojik değişiklikler tespit edildi. Aynı zamanda K40 hariç tüm gruplarda yapılan ışık mikroskobik incelemelerde histolojik değişiklikler gözlendi. Çalışma grupları ile kontrol gruplarının insülin ve glukagon immün-pozitiflikleri karşılaştırıldığında, ...

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Ketamine treatment affects hippocampal but not cortical mitochondrial function in prepubertal rats

Czerniczyniec

Karadayian

Bustamante

et al. 2020

Intl J of Devlp Neuroscience

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Previous reports have shown that ketamine triggered apoptosis in immature developing brain involving mitochondrial‐mediated pathways. However, no data for ketamine effects on hippocampal and cortical mitochondrial function are available in prepubertal rats. Twenty‐one‐day‐old Sprague–Dawley rats received ketamine (40 mg/kg i.p.) for 3 days and were killed 24 hr after the last injection. Hippocampal mitochondria from ketamine‐treated rats showed decreased malate‐glutamate state 4 and 3 respiratory rates and an inhibition in complex I and IV activities. Hippocampal mitochondrial membrane depolarization and mitochondrial permeability transition induction were observed. This was not reflected in an increment of H2O2 production probably due to increased Mn‐SOD and catalase activities, 24 hr after treatment. Interestingly, increased H2O2 production rates and cardiolipin oxidation were found in hippocampal mitochondria shortly after ketamine treatment (45 min). Unlike the hippocampus, ketamine did not affect mitochondrial parameters in the brain cortex, being the area less vulnerable to suffer ketamine‐induced oxidative damage. Results provide evidences that exposure of prepubertal rats to ketamine leads to an induction of mitochondrial ROS generation at early stages of treatment that was normalized by the triggering of antioxidant systems. Although hippocampal mitochondria from prepubertal rats were capable of responding to the oxidative stress, they remain partially dysfunctional.

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The Toxic Effects of S(+)-Ketamine on Differentiating Neurons In Vitro as a Consequence of Suppressed Neuronal Ca2+ Oscillations

Cited by 51 publications

References 30 publications

Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons

Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons

The Effects of Long Term Ketamine Use on Pancreatic Islet Cells

Ketamine treatment affects hippocampal but not cortical mitochondrial function in prepubertal rats

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