Esketamine: Less Drowsiness, More Analgesia

Anesthesia & Analgesia, Год журнала: 2024, Номер unknown

Опубликована: Янв. 31, 2024

Racemic ketamine is a 1:1 mixture of 2 enantiomers that turn light in opposite direction: Dextrorotatory esketamine approximately 4 times more affine for the N-methyl-D-aspartate (NMDA) receptor than levorotatory arketamine, which may explain why about twice as potent an analgesic and anesthetic racemate. Esketamine has attracted renewed interest view opioid crisis, racemic ketamine's abuse, esketamine's approval expanded use. We evaluated anesthesia literature concerning mental, cardiovascular, cerebral, antinociceptive effects published English between 1980 2022. The review shows are not "the same" at clinically equivalent dose: Psychomimetic seem to be essentially related NMDA blockade devoid unwanted mental impact. However, it probably involves less cholinergic inhibition. Cognitive disturbances during arousal, awakening, recovery from drug less, pronounced with esketamine. allows 50% dose reduction analgesia goes along higher clearance shorter time compared ketamine. In comparison placebo, cardiocirculatory stabilizing neuroprotective can seen induction, cardiac surgery, sedation brain injury. Evidence efficacy inconsistent, although recent meta-analysis reports improved pain relief after surgery study short observation time. To better define place, direct head-to-head racemate equi-analgesic/anesthetic warranted.

Язык: Английский

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Acute-Phase Recording of the Spreading Depolarization Continuum in Aged Nonhuman Primates During Focal Ischemic Stroke

Stroke, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

BACKGROUND: Decades of experimental and clinical data revealed that spreading depolarizations (SDs) play a central causal role in the development cortical lesions after acute brain injury. However, documentation events at onset focal ischemic stroke during initial phase injury is lacking because electroencephalography monitoring SD typically starts hours or days later. Here, we used nonhuman primates to map electrophysiological pathology through stroke’s stage. METHODS: Craniotomies were performed over both hemispheres on 4 male 1 female nemestrina rhesus macaques aged 23 years 32 years. Subdural electrode arrays placed bilaterally middle cerebral artery territory, recording from 24 electrodes cm apart left cortex 7 right. After 30 minutes baseline monitoring, and, some cases, also internal carotid anterior arteries permanently occluded with aneurysmal clips. RESULTS: Repetitive SDs occurred next 3 hours, followed by terminal euthanasia. No epileptiform activity was observed any 5 animals. Nonspreading electrical silence developed core within seconds onset, SD-initiated negative ultraslow potential several minutes. These defined led histologically confirmed cell damage. Initial subsequent transient caused depression spontaneous normally perfused surrounding without signs histological Cardiocirculatory arrest end experiments first induced nonspreading eventually, potential, which indicated death. CONCLUSIONS: Results gyrencephalic hold significant implications for understanding translation diagnosis pathologies manifested continuum.

Язык: Английский

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Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(6), С. 2179 - 2179

Опубликована: Март 11, 2023

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority trialed monotherapies to date have failed demonstrate significant benefit. It has been suggested that this due complex pathophysiology TBI, which may possibly be addressed by combination therapeutic interventions. In article, we reviewed combinations different pharmacologic treatments, non-pharmacologic interventions, combined interventions for TBI. Both preclinical clinical studies included. While promising results found in animal models, trials therapies not yet shown clear This their application without consideration evolving Improvements paradigm come from novel guided multimodal neuromonitoring imaging techniques, as well multi-targeted endogenous therapies. There also needs greater representation female subjects studies.

Язык: Английский

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Memantine inhibits cortical spreading depolarization and improves neurovascular function following repetitive traumatic brain injury

Science Advances, Год журнала: 2023, Номер 9(50)

Опубликована: Дек. 13, 2023

Cortical spreading depolarization (CSD) is a promising target for neuroprotective therapy in traumatic brain injury (TBI). We explored the effect of NMDA receptor antagonism on electrically triggered CSDs healthy and brain-injured animals. Rats received either one moderate or four daily repetitive mild closed head impacts (rmTBI). Ninety-three animals underwent craniectomy with electrocorticographic (ECoG) local blood flow monitoring. In animals, ketamine memantine inhibited 44 to 88% 50 67% cases, respectively. Near-DC/AC-ECoG amplitude was reduced by 75% 52 67%, duration 39 87% 61 78%, Daily significantly depression oligemia following CSD. Animals ( N = 31) were randomized (10 mg/kg) saline neurobehavioral testing. Memantine-treated had higher neurological scores. demonstrate that improved neurovascular function CSD sham Memantine also prevented decline blinded, preclinical rmTBI trial.

Язык: Английский

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Characterization of spreading depolarizations in swine following superior sagittal sinus occlusion: a novel gyrencephalic model study

Thrombosis Journal, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 12, 2025

Abstract Cerebral sinus thrombosis, which constitutes a small percentage of all strokes, usually affects young individuals and can lead to venous stroke. Ischemic hemorrhagic Stroke are associated with Spreading Depolarization (SD) waves in brain tissue, propagate through the affected areas cause transient disruption ionic homeostasis neuronal function. This interaction highlights complexity neurological consequences SD. In this study, we investigated occurrence SDs following occlusion superior sagittal (SSS) gyrencephalic model, specifically swine. To instigate an occlusion, surgically clipped middle third SSS. The animals were grouped monitored using one three methods: electrocorticography (ECoG) alone, ECoG intrinsic optical signal (IOS) imaging, or conjunction laser speckle contrast oxygen imaging (LSCI). Post-mortem, brains analyzed 2,3,5-triphenyl tetrazolium chloride (TTC) staining check for infarction. Our results confirmed spontaneous swine after SSS was detectable via monitoring methodologies. SD activity most frequent first hour post-occlusion, subsequently diminishing. IOS identified four unique hemodynamic responses, while TTC indicated no research is document laying groundwork future investigations both animal models human clinical studies.

Язык: Английский

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Graphene Micro-transistor Arrays Reveal Perfusion-Dependent Electrophysiological and Haemodynamic Signatures of Cortical Spreading Depolarizations in Ischaemic Stroke

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Abstract Cortical spreading depolarizations (CSDs) are large-scale disruptions of neuronal homeostasis that contribute to secondary injury in ischaemic stroke. In healthy cortex, CSDs induce vasodilation meet metabolic demand, whereas tissue, they can provoke vasoconstriction and sustained hypoperfusion, exacerbating damage. We present a multimodal neurotechnology platform integrating flexible, transparent graphene solution-gated field-effect transistor (gSGFET) arrays with laser speckle contrast imaging (LSCI), enabling simultaneous DC-coupled electrophysiological recordings cerebral blood flow high spatiotemporal fidelity. gSGFETs enable stable, distortion-free recording infraslow potentials essential for resolving CSD waveforms vivo. two murine stroke models, we show waveform duration morphology scale local perfusion, delineating subtypes predictive tissue viability haemodynamic response. metabolically compromised exhibit double peaks or negative ultraslow components result vasoconstriction, contrasting narrow, monophasic eliciting regions. Systemic ketamine shortens converts perfusion-deficit revealing mechanism its neuroprotective action. This enables high-fidelity investigation brain–blood interactions

Язык: Английский

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Monitoring Cortical Spreading Depolarization: Advancements and Applications in Neurocritical Care: A Scoping Review

Synapse, Год журнала: 2025, Номер 79(4)

Опубликована: Май 29, 2025

ABSTRACT Cortical spreading depolarization (CSD) describes a slow, sustained within the cerebral gray matter that renders neurons unable to fire action potentials, resulting in widespread neuronal depression. CSD has been observed stroke, subarachnoid hemorrhage, epilepsy, traumatic brain injury, and migraines is potential indicator of imminent death. Therefore, identification, monitoring, treatment are crucial both neurointensive care neurosurgical settings. Such measures paramount for optimizing outcomes among patients with neurological injuries. However, this slow‐spreading at high amplitudes presents challenges identifying monitoring clinical We aim identify various current techniques neurocritical settings, alongside exploring available modalities. also analyze limitations detection CSD, including identification biomarkers. A brief comprehensive scoping review literature utilizing search engines such as PubMed Google Scholar was conducted using key terms “cortical depression”, “CSD”, “spreading depolarization”, “CSD monitoring”. Eligibility restricted full‐text, English, peer‐reviewed articles. There were no restrictions on publication dates. Around 450 articles discussing reviewed ultimately 65 included analysis. Electrocorticography (ECoG), an invasive modality involves placing electrodes tissue directly, remains primary detect neurosciences intensive unit (NSICU) during procedures. there other modalities Electroencephalogram (EEG), pressure reactivity index (PRx), magnetoencephalography (MEG), MRI/fMRI, laser speckle imaging (LSI). These methods have tested animal models and/or practice but each drawbacks render these not readily or nonfunctional independent NSICU. Nevertheless, multimodal approach combination ECoG conjunction tools measure vascular response perfusion pressure, blood flow, PRx could provide timely measurements CSD. biomarkers being studied early which include adenosine, GFAP, lactate, IL‐6, TNF‐alpha. Some inhibit halt include: topiramate, valproate, propranolol, amitriptyline, methysergide, Propofol, glutamate receptor inhibitors. Although several studied, gold standard detection. currently reliable non‐invasive utilizes different prove useful tool NSICU well Further research needed only determine utility application setting explore methods.

Язык: Английский

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Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage

Neurocritical Care, Год журнала: 2023, Номер 39(1), С. 135 - 144

Опубликована: Янв. 25, 2023

Spreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, association between SD occurrence and cerebrovascular pressure reactivity as a surrogate cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using long-pressure index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH).A retrospective study aSAH who were recruited at two centers, Heidelberg (HD) Berlin (BE), was performed. Continuous monitoring mean arterial (MAP) intracranial (ICP) recorded. ICP measured an intraparenchymal probe HD measure BE through external ventricular drainage. Electrocorticographic (ECoG) activity continuously recorded 3 13 days after hemorrhage. Autoregulation according L-PRx calculated moving linear Pearson's correlation 20-min averages MAP ICP. For every identified SD, 60-min intervals averaged, plotted, depending on occurrence. Random recording periods without served control.A total 19 (HD n = 14, 5, age 50.4 years, 9 female patients) monitored for duration 230.4 h (range 96-360, STD ± 69.6 h), which ECoG recordings revealed number 277 SDs. Of these, 184 represented single 93 presented clusters. In patients, values 0.12 (95% confidence interval [CI] 0.11-0.13) 0.07 CI 0.06-0.08) control (p < 0.001). Similarly, higher value 0.11 0.11-0.12) detected than that (0.08, 95% 0.07-0.09; p more detailed analysis, changes registered clustered characterized by signs severely impaired (L-PRx clusters: 0.23 [95% 0.20-0.25]; SD: 0.09 0.08-0.10]; periods: 0.06-0.08]; This group also showed significant increases clusters compared periods.Neuromonitoring simultaneous assessment events is feasible. associated indicative disturbances. An found when probe. preliminary validates use indices evaluate disturbances Our results warrant further investigation larger prospective patient cohorts.

Язык: Английский

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Mild hypothermia reduces spreading depolarizations and infarct size in a swine model

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2023, Номер 43(6), С. 999 - 1009

Опубликована: Фев. 1, 2023

Spreading depolarizations (SDs) have been linked to infarct volume expansion following ischemic stroke. Therapeutic hypothermia provides a neuroprotective effect after This study aimed evaluate the of on propagation SDs and in an swine model. Through left orbital exenteration, middle cerebral arteries were surgically occluded (MCAo) 16 swine. Extensive craniotomy durotomy performed. Six hypothermic five normothermic animals included analysis. An intracranial temperature probe was placed right frontal subdural. One hour onset, mild induced eighteen hours electrocorticographic (ECoG) intrinsic optical signal (IOS) recordings acquired. Postmortem, 4 mm-thick slices stained with 2,3,5-triphenyltetrazolium chloride estimate volume. Compared normothermia (36.4 ± 0.4°C), (32.3 0.2°C) significantly reduced frequency (ECoG: 3.5 2.1, 73.2 5.2% vs. 1.0 0.7, 41.9 21.8%; IOS 3.9 0.4, 87.6 12.0% 1.4 67.7 8.3%, respectively). Further, among (23.2 1.8% 32.4 2.5%) reduced. reduces ischemia.

Язык: Английский

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Nonpharmacological modulation of cortical spreading depolarization

Life Sciences, Год журнала: 2023, Номер 327, С. 121833 - 121833

Опубликована: Июнь 10, 2023

Язык: Английский

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