1. Ac-FLTD-CMK inhibits pyroptosis and exerts neuroprotective effect in a mice model of traumatic brain injury.
- Author
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Wang P, Pan B, Tian J, Yang L, Chen Z, Yang L, and Fan Z
- Subjects
- Animals, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Brain metabolism, Brain Injuries, Traumatic metabolism, Caspase 1 drug effects, Caspase 1 metabolism, Caspase 3 drug effects, Caspase 3 metabolism, Caspases, Initiator drug effects, Caspases, Initiator metabolism, Disease Models, Animal, Interleukin-18 metabolism, Interleukin-1beta drug effects, Interleukin-1beta metabolism, Intracellular Signaling Peptides and Proteins drug effects, Intracellular Signaling Peptides and Proteins metabolism, Mice, Neurons drug effects, Neurons metabolism, Open Field Test, Phosphate-Binding Proteins drug effects, Phosphate-Binding Proteins metabolism, Rotarod Performance Test, Brain drug effects, Brain Contusion metabolism, Caspase Inhibitors pharmacology, Neuroprotective Agents pharmacology, Pyroptosis drug effects
- Abstract
Pyroptosis has been reported to contribute to the traumatic brain injury (TBI) process. Ac-FLTD-CMK is a newly synthesized pyroptosis inhibitor. However, whether Ac-FLTD-CMK inhibits pyroptosis and plays a neuroprotective role after TBI is unknown. The present study aimed to determine the effects of Ac-FLTD-CMK on TBI in a mouse model. Male C57BL/6 mice were randomly divided into sham, TBI + vehicle, and TBI + Ac-FLTD-CMK groups. TBI was induced using a weight-drop apparatus. Intraventricular injection of Ac-FLTD-CMK was performed 30 min after TBI. Caspase-1, caspase-11, gasdermin-D (GSDMD), and caspase-3 expression in the peri-contusional cortex were assessed by western blotting. Interleukin-1β (IL-1β) and interleukin-18 (IL-18) expression in the peri-contusional cortex were measured using ELISA. Behavioral experiments, brain water content, Evans blue extravasation, lactate dehydrogenase (LDH) release, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were also performed. The results showed that Ac-FLTD-CMK administration significantly downregulated caspase-1 p20, caspase-11 p20, GSDMD N-terminal, IL-1β, and IL-18 expression; reduced LDH release; alleviated neuronal death; attenuated brain edema and blood-brain barrier damage; and improved neurobehavioral function. These findings indicate that Ac-FLTD-CMK treatment suppresses pyroptosis and protects mice against TBI., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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