The Influence of Droperidol, Diazepam, and Physostigmine on Ketamine-induced Behavior and Brain Regional Glucose Utilization in Rat

Oguchi, Katsuji; Arakawa, Kasumi; Nelson, Stanley R.; Samson, Frederick E.

doi:10.1097/00000542-198211000-00001

Cited by 39 publications

(12 citation statements)

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“…In humans, CMR is increased in the frontomedial and anterior cingulate cortex, but decreased in other regions [15]. Similar region-specific effects of ketamine have been reported in the rat [16]. Nitrous oxide (N 2 O) can cause a major CMR increase when given alone, although this may be dose and species dependent [17, 18].…”

Section: Resting Cerebral Blood Flow and Metabolismmentioning

confidence: 96%

Anesthesia in Experimental Stroke Research

Hoffmann

Sheng

Ayata

et al. 2016

Transl. Stroke Res.

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Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke.

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Section: Resting Cerebral Blood Flow and Metabolismmentioning

confidence: 96%

Anesthesia in Experimental Stroke Research

Hoffmann

Sheng

Ayata

et al. 2016

Transl. Stroke Res.

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“…), it caused marked hyperactivity in limbic structures, especially the hippocampus, and this is an undesirable side-effect. 38 -42 We have shown hippocampal activation by using anesthetic doses of ketamine 42,43 and neuroprotective doses of MK-801 (unpublished) in LCGU studies. Others have shown this for PCP.…”

Section: Agents That Lower the Threshold To Cholinergic Seizuresmentioning

confidence: 98%

Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins

et al. 2001

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Soman, a potent acetylcholinesterase inhibitor, induces status epilepticus in rats followed by conspicuous neuropathology, most prominent in piriform cortex and the CA3 region of the hippocampus. Cholinergic seizures originate in striatal-nigral pathways and with fast-acting agents (soman) rapidly spread to limbic related areas and finally culminate in a full-blown status epilepticus. This leads to neurochemical changes, some of which may be neuroprotective whereas others may cause brain damage. Pretreatment with lithium sensitizes the brain to cholinergic seizures. Likewise, other agents that increase limbic hyperactivity may sensitize the brain to cholinergic agents. The hyperactivity associated with the seizure state leads to an increase in intracellular calcium, cellular edema and metal delocalization producing an oxidative stress. These changes induce the synthesis of stress-related proteins such as heat shock proteins, metallothioneins and heme oxygenases. We show that soman-induced seizures cause a depletion in tissue glutathione and an increase in tissue 'catalytic' iron, metallothioneins and heme oxygenase-1. The oxidative stress induces the synthesis of stress-related proteins, which are indicators of 'stress' and possibly provide neuroprotection. These findings suggest that delocalization of iron may catalyze Fenton-like reactions, causing progressive cellular damage via free radical products. Published in

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“…The excessive release of neurotransmitters and subsequent overexcitation also might underlie the ability of NMDA antagonists (eg MK801, ketamine and PCP) to increase metabolism in several corticolimbic regions. [55][56][57][58][59][60][61][62][63][64][65][66][67][68] If the NRHypo circuitry is present in several corticolimbic regions, why then does the reversible neurotoxicity appear only in the RSC and not in the other regions? Because the dose response curve for inducing the neurotoxicity in the RSC is an inverted U-shape ( Figure 5), we suspect that the selectivity of the reversible neurotoxicity for the RSC is a function of the relative stimulation of the muscarinic vs non-NMDA receptor.…”

Section: Molecular Psychiatrymentioning

confidence: 99%

Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity

et al. 2002

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NMDA glutamate receptor antagonists are used in clinical anesthesia, and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer's disease and schizophrenia. Thus, understanding the mechanism underlying NRHypo-induced neurotoxicity and psychosis could have significant clinically relevant benefits. NRHypo neurotoxicity can be prevented by several classes of agents (eg antimuscarinics, non-NMDA glutamate antagonists, and ␣ 2 adrenergic agonists) suggesting that the mechanism of neurotoxicity is complex. In the present study a series of experiments was undertaken to more definitively define the receptors and complex neural circuitry underlying NRHypo neurotoxicity. Injection of either the muscarinic antagonist scopolamine or the non-NMDA antagonist NBQX directly into the cortex prevented NRHypo neurotoxicity. Clonidine, an ␣ 2 adrenergic agonist, protected against the neurotoxicity when injected into the basal forebrain. The combined injection of muscarinic and non-NMDA Glu agonists reproduced the neurotoxic reaction. Based on these and other results, we conclude that the mechanism is indirect, and involves a complex network disturbance, whereby blockade of NMDA receptors on inhibitory neurons in multiple subcortical brain regions, disinhibits glutamatergic and cholinergic projections to the cerebral cortex. Simultaneous excitotoxic stimulation of muscarinic (m 3 ) and glutamate (AMPA/kainate) receptors on cerebrocortical neurons appears to be the proximal mechanism by which the neurotoxic and psychotomimetic effects of NRHypo are mediated.

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The Influence of Droperidol, Diazepam, and Physostigmine on Ketamine-induced Behavior and Brain Regional Glucose Utilization in Rat

Cited by 39 publications

References 0 publications

Anesthesia in Experimental Stroke Research

Anesthesia in Experimental Stroke Research

Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins

Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity

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