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Protein nanoparticles induce the activation of voltage-dependent non-selective ion channels to modulate biological osmotic pressure in cytotoxic cerebral edema.
Fan, Wei; Liu, Liming; Yin, Yuxuan; Zhang, Jiayi; Qiu, Zhaoshun; Guo, Jun; Li, Guangming.
Afiliación
  • Fan W; Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, China.
  • Liu L; School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • Yin Y; Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, China.
  • Zhang J; Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, China.
  • Qiu Z; School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • Guo J; School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • Li G; Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, China.
Front Pharmacol ; 15: 1361733, 2024.
Article en En | MEDLINE | ID: mdl-39130645
ABSTRACT

Introduction:

Cytotoxic cerebral edema is a serious complication associated with cerebral ischemic stroke and is widely treated using the hypertonic dehydrant. Here, we propose, for the first time, the decrease of intracellular osmosis as a treatment strategy for alleviating cytotoxic cerebral edema.

Methods:

We established a fluorescence resonance energy transfer-based intermediate filament tension probe for the study and in situ evaluation of osmotic gradients, which were examined in real-time in living cells from primary cultures as well as cell lines. The MCAO rat model was used to confirm our therapy of cerebral edema.

Results:

Depolymerization of microfilaments/microtubules and the production of NLRP3 inflammasome resulted in an abundance of protein nanoparticles (PNs) in the glutamate-induced swelling of astrocytes. PNs induced changes in membrane potential and intracellular second messengers, thereby contributing to hyper-osmosis and the resultant astrocyte swelling via the activation of voltage-dependent nonselective ion channels. Therefore, multiple inhibitors of PNs, sodium and chloride ion channels were screened as compound combinations, based on a decrease in cell osmosis and astrocyte swelling, which was followed by further confirmation of the effectiveness of the compound combination against alleviated cerebral edema after ischemia.

Discussion:

The present study proposes new pathological mechanisms underlying "electrophysiology-biochemical signal-osmotic tension," which are responsible for cascade regulation in cerebral edema. It also explores various compound combinations as a potential treatment strategy for cerebral edema, which act by multi-targeting intracellular PNs and voltage-dependent nonselective ion flux to reduce astrocyte osmosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
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: Front Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza