Evaluation of neurotoxicity and long-term function and behavior following intrathecal 1 % 2-chloroprocaine in juvenile rats

Walker, Suellen M.; Malkmus, Shelle; Eddinger, Kelly A.; Steinauer, Joanne; Roberts, Amanda J.; Shubayev, Veronica I.; Grafe, Marjorie R.; Powell, Susan B.; Yaksh, Tony L.

doi:10.1016/j.neuro.2021.11.010

Cited by 3 publications

(3 citation statements)

References 88 publications

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“…Some studies have used intrathecal injection of local anesthetics to observe their neurotoxicity. 13,14,17 This study injected local anesthetics around the sciatic nerve, which is similar to the clinical peripheral nerve block method, directly simulating the occurrence of peripheral neurotoxicity of local anesthetics in clinical practice. Ropivacaine hydrochloride is the most widely used local anesthetic for nerve block in the clinic at present, and the concentration used in the clinic varies from 0.1 to 1%.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Many studies are also based on in vitro cell culture models, and their research results cannot be fully applied to whole animals. In the past, the neurotoxicity experiment of local anesthetics in the whole animal experiment was usually based on the method of intrathecal injection of local anesthetics, 13,14 and its main research sites were in the spinal cord and dorsal root ganglion. At present, there is no ideal animal model of peripheral neurotoxicity injury caused by local anesthetics.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of an animal model of sciatic nerve injury induced by local anesthetics

Liang

et al. 2023

Hum Exp Toxicol

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Peripheral neurotoxicity injury caused by local anesthetics is a common complication of clinical anesthesia. The study of its mechanism is helpful to prevent and treat the neurotoxic injury of local anesthetics. Previous studies on peripheral neurotoxicity injury caused by local anesthetics have mainly focused on in vitro cell experiments. Due to the lack of an animal model of peripheral neurotoxicity damage caused by local anesthetics, there are few in vivo experimental studies regarding this topic. Herein, 1% ropivacaine hydrochloride was injected into the sciatic nerve by direct incision and exposure of the sciatic nerve to create a local anesthetic neurotoxic injury model. The results showed that 1% ropivacaine hydrochloride could reduce the lower limb motor score and mechanical paw withdrawal threshold in mice 48 hours after injection. Pathological sections showed that 48 hours after treatment with 1% ropivacaine hydrochloride, the sciatic nerve showed increased axonal edema and degeneration, edema between nerve fiber bundles, increased degeneration of axon and myelin sheath vacuoles, edema of nerve bundle membrane and local degeneration and necrosis, and a large number of inflammatory cells around the nerve adventitia were soaked. The above results show that under open vision, 1% ropivacaine hydrochloride can cause injury to the sciatic nerve after 48 h of treatment, which can simulate the neurotoxic damage of local anesthetics. This animal model provides a research tool for studying the mechanism of neurotoxic injury caused by local anesthetics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Establishment of an animal model of sciatic nerve injury induced by local anesthetics

Liang

et al. 2023

Hum Exp Toxicol

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“…Although the indications are largely confined to surgical procedures involving the lower part of the body, spinal anesthesia might be an important substitute to GA in select clinical scenarios. While the available data advise caution with regard to local anesthetics causing neuronal damage [128], preclinical evidence so far has disproven the hypothesis of heightened neuroapoptosis following spinal anesthesia in rat neonates [129][130][131]. Furthermore, two clinical studies have demonstrated the feasibility and safety of spinal anesthesia for early-life surgical procedures [132,133].…”

Section: The Timing Of Ga Exposure and Regional Anesthesiamentioning

confidence: 99%

Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?

Useinovic

Maksimovic

Near

et al. 2022

IJMS

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Since its invention, general anesthesia has been an indispensable component of modern surgery. While traditionally considered safe and beneficial in many pathological settings, hundreds of preclinical studies in various animal species have raised concerns about the detrimental and long-lasting consequences that general anesthetics may cause to the developing brain. Clinical evidence of anesthetic neurotoxicity in humans continues to mount as we continue to contemplate how to move forward. Notwithstanding the alarming evidence, millions of children are being anesthetized each year, setting the stage for substantial healthcare burdens in the future. Hence, furthering our knowledge of the molecular underpinnings of anesthesia-induced developmental neurotoxicity is crucially important and should enable us to develop protective strategies so that currently available general anesthetics could be safely used during critical stages of brain development. In this mini-review, we provide a summary of select strategies with primary focus on the mechanisms of neuroprotection and potential for clinical applicability. First, we summarize a diverse group of chemicals with the emphasis on intracellular targets and signal-transduction pathways. We then discuss epigenetic and transgenerational effects of general anesthetics and potential remedies, and also anesthesia-sparing or anesthesia-delaying approaches. Finally, we present evidence of a novel class of anesthetics with a distinct mechanism of action and a promising safety profile.

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A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity

Borzage,

Peterson

2024

Anesthesia &Amp; Analgesia

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Although anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of this scoping review was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings.

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Evaluation of neurotoxicity and long-term function and behavior following intrathecal 1 % 2-chloroprocaine in juvenile rats

Cited by 3 publications

References 88 publications

Establishment of an animal model of sciatic nerve injury induced by local anesthetics

Establishment of an animal model of sciatic nerve injury induced by local anesthetics

Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?

A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity

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