Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

Dhote, Franck; Carpentier, Pierre; Barbier, Laure; Peinnequin, André; Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie; Dorandeu, Frédéric

doi:10.1016/j.taap.2011.12.024

Cited by 50 publications

(51 citation statements)

References 90 publications

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“…In both animal experiments and human observation, ketamine also prevents the general antipro-inflammatory mechanisms to excessively overcome the pro-inflammatory influences [96] . Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after toxic status epilepticus in mice [97] . In a systematic review of clinical studies, the authors concluded that intraoperative ketamine exerts anti-inflammatory effects [98] .…”

Section: Anti-inflammationmentioning

confidence: 99%

Ketamine use in current clinical practice

2016

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After nearly half a century on the market, ketamine still occupies a unique corner in the medical armamentarium of anesthesiologists or clinicians treating pain. Over the last two decades, much research has been conducted highlighting the drug's mechanisms of action, specifically those of its enantiomers. Nowadays, ketamine is also being utilized for pediatric pain control in emergency department, with its anti-hyperalgesic and anti-inflammatory effects being revealed in acute and chronic pain management. Recently, new insights have been gained on ketamine's potential anti-depressive and antisuicidal effects. This article provides an overview of the drug's pharmacokinetics and pharmacodynamics while also discussing the potential benefits and risks of ketamine administration in various clinical settings.

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Section: Anti-inflammationmentioning

confidence: 99%

Ketamine use in current clinical practice

2016

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“…With the limitations of a simple mRNA study, brain inflammation was also suggested by a reduction in the content of IkBa mRNA that can be used to evaluate NFkB gene activation (Barbier et al, 2009), well in line with the description of the various inflammatory pathways that are modified following soman poisoning (Dhote et al, 2007;Dillman et al, 2009;Williams et al, 2003), such changes being confirmed by the increase in some of the related coded proteins in several brain areas (Dhote et al, 2012). Conversely, little is known regarding the modulation of the brain neurotrophin expression following soman intoxication.…”

Section: Discussionmentioning

confidence: 97%

“…The dose of ketamine was chosen based on what might be required for the treatment of OPinduced SE/RSE: 75 mg kg À1 , an anesthetic dose for rats. In other species, an anesthetic dose of ketamine combined with atropine sulfate was indeed proven to be protective against OP-induced brain lesions in guinea-pigs (Dorandeu et al, 2005 and mice (Dhote et al, 2012). Ketamine used at 75 mg kg À1 was also suggested to reduce the side effects of atropine sulfate in heatexposed rats .…”

Section: Drugsmentioning

confidence: 99%

“…After soman injection, signs and symptoms, including hypersalivation and development of convulsions, were continuously monitored. Although our current paradigm did not include electroencephalographic recordings, we previously showed that there was a close relationship between the occurrence of long-lasting convulsions and the development of SE in mice (Dhote et al, 2012;Testylier et al, 2007). Seventy-five minutes after challenge (after ca.…”

Section: Experimental Designmentioning

confidence: 99%

“…Although ketamine administration may be accompanied by psychological side effects, such as dissociative states and hallucinations (Sinner and Graf, 2008), it does not commonly induce respiratory depression and has little effect on the cardiovascular system in humans (for review, see Dorandeu et al, 2013b and the papers published in the dedicated special issue). Furthermore the combination of ketamine and atropine sulfate exhibits an effective anticonvulsant and neuroprotectant effect in guinea-pigs (Dorandeu et al, 2005, mice (Dhote et al, 2012) and rats (Testylier et al, unpublished results), even when given 1 h after the beginning of seizures, viz. during the soman induced-RSE.…”

Section: Introductionmentioning

confidence: 99%

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Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment

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N‐methyl‐d‐aspartate receptors: Structure, function, and role in organophosphorus compound poisoning

Kolić,

Kovarik

2024

BioFactors

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Acute organophosphorus compound (OP) poisoning induces symptoms of the cholinergic crises with the occurrence of severe epileptic seizures. Seizures are induced by hyperstimulation of the cholinergic system, but are enhanced by hyperactivation of the glutamatergic system. Overstimulation of muscarinic cholinergic receptors by the elevated acetylcholine causes glutamatergic hyperexcitation and an increased influx of Ca2+ into neurons through a type of ionotropic glutamate receptors, N‐methyl‐d‐aspartate (NMDA) receptors (NMDAR). These excitotoxic signaling processes generate reactive oxygen species, oxidative stress, and activation of the neuroinflammatory response, which can lead to recurrent epileptic seizures, neuronal cell death, and long‐term neurological damage. In this review, we illustrate the NMDAR structure, complexity of subunit composition, and the various receptor properties that change accordingly. Although NMDARs are in normal physiological conditions important for controlling synaptic plasticity and mediating learning and memory functions, we elaborate the detrimental role NMDARs play in neurotoxicity of OPs and focus on the central role NMDAR inhibition plays in suppressing neurotoxicity and modulating the inflammatory response. The limited efficacy of current medical therapies for OP poisoning concerning the development of pharmacoresistance and mitigating proinflammatory response highlights the importance of NMDAR inhibitors in preventing neurotoxic processes and points to new avenues for exploring therapeutics for OP poisoning.

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Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

Cited by 50 publications

References 90 publications

Ketamine use in current clinical practice

Ketamine use in current clinical practice

Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment

N‐methyl‐d‐aspartate receptors: Structure, function, and role in organophosphorus compound poisoning

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