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Inhibition of the glutamatergic PVT-NAc projections attenuates local anesthetic-induced neurotoxic behaviors.
Zou, Yu; He, Xin; Ye, Zhiwen; Li, Zhengyiqi; Guo, Qulian; Zou, Wangyuan; Peng, Qianyi.
Afiliación
  • Zou Y; Department of Anesthesia, Xiangya Hospital Central South University, Changsha, Hunan Province, China.
  • He X; Department of Anesthesia, Xiangya Hospital Central South University, Changsha, Hunan Province, China.
  • Ye Z; Department of Critical Care Medicine, Xiangya Hospital Central South University, Changsha, Hunan Province, China.
  • Li Z; Xiangya Hospital Central South University National Clinical Research Center for Geriatric Disorders, Changsha, Hunan Province, China.
  • Guo Q; Department of Anesthesia, Xiangya Hospital Central South University, Changsha, Hunan Province, China.
  • Zou W; Department of Anesthesia, Xiangya Hospital Central South University, Changsha, Hunan Province, China.
  • Peng Q; Department of Anesthesia, Xiangya Hospital Central South University, Changsha, Hunan Province, China 405905@csu.edu.cn wangyuanzou@csu.edu.cn.
Reg Anesth Pain Med ; 2024 Jan 17.
Article en En | MEDLINE | ID: mdl-38233353
ABSTRACT

INTRODUCTION:

Local anesthetic-induced neurotoxicity contributes to perioperative nerve damage; however, the underlying mechanisms remain unclear. Here, we investigated the role of the paraventricular thalamus (PVT)-nucleus accumbens (NAc) projections in neurotoxicity induced by ropivacaine, a local anesthetic agent.

METHODS:

Ropivacaine (58 mg/kg, intraperitoneal administration) was used to construct the local anesthetic systemic toxicity (LAST) mice model. We first identified neural projections from the PVT to the NAc through the expression of a retrograde tracer and virus. The inhibitory viruses (rAAV-EF1α-DIO-hm4D(Gi)-mCherry-WPREs AAV2/retro and rAAV-CaMKII-CRE-WPRE-hGh AAV2/9) were injected into the mice model to assess the effects of the specific inhibition of the PVT-NAc pathway on neurological behaviors in the presence of clozapine-N-oxide. The inhibition of the PVT-NAc pathway was evaluated by immunofluorescence staining of c-Fos-positive neurons and Ca2+ signals in CaMKIIa neurons.

RESULTS:

We successfully identified a circuit connecting the PVT and NAc in C57BL/6 mice. Ropivacaine administration induced the activation of the PVT-NAc pathway and seizures. Specific inhibition of NAc-projecting CaMKII neurons in the PVT was sufficient to inhibit the neuronal activity in the NAc, which subsequently decreased ropivacaine-induced neurotoxicity.

CONCLUSION:

These results reveal the presence of a dedicated PVT-NAc circuit that regulates local anesthetic-induced neurotoxicity and provide a potential mechanistic explanation for the treatment and prevention of LAST.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Reg Anesth Pain Med Asunto de la revista: ANESTESIOLOGIA / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Reg Anesth Pain Med Asunto de la revista: ANESTESIOLOGIA / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido