Preliminary study on the involvement of mixed lineage kinase domain-like pseudokinase in high-altitude cerebral edema in mice
MENG Xinyu
MENG Han
MAO Zhuqing
WANG Yanjin
TAN Yanchen
WANG Yazhou
CUI Yi
YANG Qinghu
Abstract：Objective To explore the role of mixed lineage kinase domain-like pseudokinase(MLKL),a key molecule in necroptosis,in high-attitude cerebral edema(HACE)in mice.Methods Adult male C57BL/6 wild-type mice and MLKL knockout(MLKL-/-)mice were divided into three groups:control group,WT HACE group and MLKL-/-HACE group,with 8 mice in each group.Mice were placed into a small high-altitude hypoxia chamber.The altitude was adjusted to 5 500 m,and mice were exposed for 72 h to establish HACE model.The expression of MLKL was detected by Western blotting.Brain water content was adopted to assess the degree of cerebral edema.Evans blue was used to evaluate brain-blood barrier permeability.Immunofluorescence staining was used to examine the distribution of MLKL and aquaporin-4(AQP4)in blood vessels and the effusion of IgG.Novel object recognition test was used to analyze the cognitive function of mice.Results Exposure to 5 500 m for 72 h led to blood-brain barrier disruption,increased brain water content(P＜0.01),decreased novel object recognition ability(P＜0.01),increased expression of MLKL and pMLKL(P＜0.05),and dot aggregates in immunofluorescence co-labeling of pMLKL with AQP4 and CD31 in mice.MLKL-/-mice showed a lower degree of HACE under the same stimulation,manifested as a significant reduction of brain water content in MLKL-/-HACE group as compared to WT HACE group(P＜0.05),a decrease of blood-brain barrier opening,a reduction of immunoglobulin leakage from blood vessels,and an improvement of novel object recognition.Conclusion MLKL,a key molecule of necroptosis,is involved in the occurrence and development of HACE,and knockout of MLKL can alleviate HACE.
Keywords：high-altitude cerebral edemaMLKLblood-brain barriernecroptosiscytotoxic edemamouse
Publication Date：2025-04-30
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：5( 521-525 )