Isoflurane suppresses cortical spreading depolarizations compared to propofol — Implications for sedation of neurocritical care patients

Takagaki, Masatoshi; Feuerstein, Delphine; Kumagai, Tetsuya; Gramer, Markus; Yoshimine, Toshiki; Graf, Rudolf

doi:10.1016/j.expneurol.2013.11.003

Cited by 50 publications

(42 citation statements)

References 44 publications

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“…Adenosine accumulation correlated with DC durations of spontaneous SDs in dMCAO animals (peak, Spearman r = 0.6182, Po 0.01, n = 18 SDs from eight animals). Compared with other reports of dMCAO, the delay and/or prevention of SD in some of our animals was likely related to the use of isoflurane as anesthetic 39 and the intentionally elevated arterial O 2 content. 29 Twenty-eight SDs in 74.4 recording hours were detected by LSCI transients, and of these, 21 SDs were confirmed by DC shifts.…”

Section: Resultscontrasting

confidence: 79%

Spreading Depolarization-Induced Adenosine Accumulation Reflects Metabolic Status In Vitro and In Vivo

Lindquist

Shuttleworth

2014

J Cereb Blood Flow Metab

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Spreading depolarization (SD), a pathologic feature of migraine, stroke and traumatic brain injury, is a propagating depolarization of neurons and glia causing profound metabolic demand. Adenosine, the low-energy metabolite of ATP, has been shown to be elevated after SD in brain slices and under conditions likely to trigger SD in vivo. The relationship between metabolic status and adenosine accumulation after SD was tested here, in brain slices and in vivo. In brain slices, metabolic impairment (assessed by nicotinamide adenine dinucleotide (phosphate) autofluorescence and O 2 availability) was associated with prolonged extracellular direct current (DC) shifts indicating delayed repolarization, and increased adenosine accumulation. In vivo, adenosine accumulation was observed after SD even in otherwise healthy mice. As in brain slices, in vivo adenosine accumulation correlated with DC shift duration and increased when DC shifts were prolonged by metabolic impairment (i.e., hypoglycemia or middle cerebral artery occlusion). A striking pattern of adenosine dynamics was observed during focal ischemic stroke, with nearly all the observed adenosine signals in the periinfarct region occurring in association with SDs. These findings suggest that adenosine accumulation could serve as a biomarker of SD incidence and severity, in a range of clinical conditions. Keywords: acute stroke; adenosine; brain slice; electrophysiology; energy metabolism; spreading depression INTRODUCTION Spreading depolarization (SD) of brain tissue is a self-propagating wave of neuronal and glial activation, carried by large transmembrane currents that depolarize cells and disrupt ionic gradients. 1,2 Spreading depolarization imposes a large metabolic burden on brain tissue, evidenced by depletion of energy substrates and O 2 3,4 and by accumulation of metabolic byproducts such as lactate and H + . 5,6 ATP concentration drops by nearly 50% during SD in normoxic conditions, 7 and metabolic depletion is expected to be more severe when occurring in tissue with limited substrate availability.Recent clinical studies strongly suggest that SD is involved in the pathophysiology of migraine with aura, thromboembolic stroke, traumatic brain injury, and subarachnoid hemorrhage. 8 While normoxic, normoglycemic SD can be noninjurious, 9 SD in the setting of metabolic compromise exacerbates neuronal injury. 10,11 Work in animal models has identified delayed repolarization, marked by prolonged extracellular direct current (DC) shifts, as a hallmark of injurious SD in metabolically compromised tissue. 10 Observational studies in human subjects have confirmed the association between prolonged DC shifts and poor outcome after SD, 12 but human studies have so far been limited by the requirement for invasive electrical recordings in patients with craniotomies. It would be helpful to establish additional biomarkers of metabolic status, to assess vulnerability to SD in injured brain.Extracellular adenosine accumulation can serve as a global indicator of energy charge....

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Section: Resultscontrasting

confidence: 79%

Spreading Depolarization-Induced Adenosine Accumulation Reflects Metabolic Status In Vitro and In Vivo

Lindquist

Shuttleworth

2014

J Cereb Blood Flow Metab

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“…Of further interest is that SD is not observed to propagate into the thalamus for either of the FHM-1 mutations, although this propagation has been reported to occur in a percentage of S218L mice (28). It should be considered that in the study by EikermannHaerter et al (28) the electrophysiological measurements of SD were made under pentobarbital anesthesia, whereas our experiments were performed under isoflurane anesthesia; the two anesthetics may have distinct effects on SD invasion into the thalamus (35). Despite this difference, both studies indicate that the white matter of the internal capsule appears to be a particularly difficult region for SD to traverse.…”

Section: Sd Spreads To Subcortical Structures In Both Fhm-1 Strains Bmentioning

confidence: 81%

In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

Cain

Bohnet

LeDue

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wildtype (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the Ca V 2.1 (P/Q-type) calcium channel subunit, pregabalin slowed the speed of SD propagation in vivo. Acute systemic administration of pregabalin in vivo also selectively prevented the migration of SD into subcortical striatal and hippocampal regions in the R192Q strain that exhibits a milder phenotype and gain of Ca V 2.1 channel function. At the cellular level, pregabalin inhibited glutamatergic synaptic transmission differentially in WT, R192Q, and S218L mice. The study describes a DW-MRI analysis method for tracking the progression of SD and provides support and a mechanism of action for pregabalin as a possible effective therapy in the treatment of migraine.familial hemiplegic migraine type 1 | migraine | diffusion-weighted MRI | voltage-gated calcium channel | gabapentinoids

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“…Different pathways and sites of action seem to be involved and include beneficial effects on mitochondrial processes [13,14], inhibition of carboxy-terminal modulator protein [15], and activation of antioxidant enzymes [16]. In a traumatic brain injury rodent model, isoflurane administration before and during controlled trauma was better than propofol at limiting secondary neuronal injury associated with cortical spreading depolarizations [17]. Baseline blood flow and plasma glucose levels were also higher in the isoflurane group, suggesting better metabolic conditions.…”

Section: Key Pointsmentioning

confidence: 97%

Update on anesthetic neuroprotection

Zwerus

Absalom

2015

Current Opinion in Anaesthesiology

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The evidence of benefit of current strategies remains sparse. Given the complex pathophysiology of cerebral ischemia and hypoxia, a multimodal approach to neuroprotective strategies seems sensible. The many variables and confounds associated with the clinical setting of patients, their comorbidities and concurrent medications, pose challenges to translate from experimental studies to clinical practice.

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Isoflurane suppresses cortical spreading depolarizations compared to propofol — Implications for sedation of neurocritical care patients

Cited by 50 publications

References 44 publications

Spreading Depolarization-Induced Adenosine Accumulation Reflects Metabolic Status In Vitro and In Vivo

Spreading Depolarization-Induced Adenosine Accumulation Reflects Metabolic Status In Vitro and In Vivo

In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

Update on anesthetic neuroprotection

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