Neuroprotective effect of AG490 in experimental traumatic brain injury of rats.
BACKGROUND
Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI.


METHODS
Sprague Dawley rats (n = 240) were randomly divided into a sham operation group, TBI+saline group and TBI+AG490 (JAK/STAT inhibitor) group. Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score (NSS) was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry.


RESULTS
In both the TBI+saline group and the TBI+AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the period investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group.


CONCLUSIONS
Inhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.
Department of Neurosurgery, Affiliated Hospital of Weifang Medical College, Weifang, Shandong 261031, China.
Ai-ling
AL
DU
Tai-ling
TL
Ji
Bin
B
Yang
Jian-feng
JF
Cao
Xing-guang
XG
Zhang
Yu
Y
Li
Shun
S
Pan
Bo
B
Zhang
Zhen-bo
ZB
Hu
Xian-wei
XW
Zeng
D000818:Animals; D001929:Brain Edema / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy*; D019013:CD40 Antigens / Q000032:analysis; D005434:Flow Cytometry; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050791:STAT Transcription Factors / Q000378:metabolism; D020032:Tyrphostins / Q000627:therapeutic use*
D019013:CD40 Antigens; D018696:Neuroprotective Agents; D050791:STAT Transcription Factors; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053612:Janus Kinases