Myeloid-epithelial-reproductive tyrosine kinase regulates microglial M1/M2 polarization after traumatic brain injury to alleviate neurological damage
HUO Da
HAN Yu-wei
WANG Chen-chen
JIN Hai
LI Xiao-ming
Abstract：Objective To investigate the role of myeloid-epithelial-reproductive tyrosine kinase(MerTK)in regulating microglial M1/M2 polarization and neuroinflammation following traumatic brain injury(TBI).Methods A total of 25 male sprague-dawley rats,8 to 10 weeks old,body weight(300±30)g,ranging from 270 to 330 g.Rats were randomly divided into sham group(n=5),TBI group(n=10),TBI+negative control siRNA group(n=5),and TBI+MerTK siRNA group(n=5)by random number table method.In addition to sham operation group,other groups were subjected to controlled cortical impact to establish TBI models.MerTK expression was inhibited via siRNA injection.Quantitative real-time polymerase chain reaction(PCR)was used to measure mRNA levels of CD16(M1 marker)and CD206(M2 marker).Western blot was used to assess MerTK mRNA and protein expression.Immunofluorescence staining was uesd to quantify CD16 and CD206 cells.Modified neurological severity score(mNSS)was used to evaluate neurological function.Brain water content was measured.Results The levels of CD16 mRNA and CD206 mRNA,as well as the levels of MerTK mRNA and MerTK protein expression in the damaged cortex of the rats in the TBI group were higher than those in the sham-operated group at 12 h and 3 d,the differences were statistically significant(P<0.05).After 3 days of surgery,the MerTK protein level in the TBI+MerTK siRNA group was lower than that in the TBI+negative control siRNA group and the TBI group,the difference was statistically significant(P<0.05).The proportion of CD16-positive cells in the TBI+MerTK siRNA group was higher than that in the TBI group,and the proportion of CD206-positive cells was lower than that in the TBI group,the difference was statistically significant(P<0.05).After 3 days of surgery,The mNSS score of rats in TBI+MerTK siRNA group was higher than that of TBI group and TBI+negative control siRNA group,the difference was statistically significant(P<0.05).The degree of brain tissue oedema in TBI+MerTK siRNA group was higher than that of TBI group,the difference was statistically significant(P<0.05).Conclusion MerTK expression in brain tissue after TBI is up-regulated and regulates the M1/M2 balance in microglia,and inhibition of MerTK expression decreases M2 polarisation and increases pro-inflammatory M1-type polarisation,exacerbating cerebral oedema and neurological impairment.
Keywords：traumatic brain injurymicrogliamyeloid-epithelial-reproductive tyrosine kinase
Publication Date：2025-09-25
Online Publishing Date：2025-11-06(First online date of this platform, not the publication date of the document)
Pages：5( 326-330 )