[Neuroprotective effects of combined application of JAK-STAT signal pathway inhibitor and free radical scavenger on focal cerebral ischemia/reperfusion injury in rats].
OBJECTIVE
To investigate the neuroprotective effects and dose-response relation by combining JAK-STAT signal pathway inhibitor (AG490) with free radical scavenger dimethylthiourea (DMTU) in rats subjected to focal cerebral ischemia/reperfusion (I/R) injury.


METHODS
In all rats, the middle cerebral artery occlusion (MCAO) was produced by occlusion of right internal carotid artery with a nylon monofilament. One hundred male Sprague-Dawley (SD) rats were divided into ten groups according to random digits table, 10 rats were in each group. The first experiment involved I/R model control, dimethyl sulfoxide (DMSO) control, normal saline (NS) control, AG490, DMTU and combination of AG490 and DMTU (A+D) groups. The second experiment involved model group and three experimental groups in which various doses of DMTU and AG490 were administered. The neurological behavior scores (NBS) were assessed at 24, 48 and 72 hours after reperfusion respectively in both experiments, and all the animals were then decapitated to determine the brain infarct volume after 72 hours.


RESULTS
The values of NBS in A+D group, AG490 group and DMTU group were higher than those in model group at 24, 48 and 72 hours after I/R, and their brain infarct volumes were obviously smaller than model group as well (all P<0.05). The brain infarct volume in A+D group was obviously smaller compared with AG490 and DMTU alone (all P<0.05). The values of NBS were higher and the brain infarct volumes were smaller in both high dose and medium dose combination groups than those in low dose combination and model groups respectively (all P<0.05). In addition, brain infarct volumes in high dose group were smaller than medium dose group (P<0.05), but there was no statistically significant difference between low dose and model groups.


CONCLUSIONS
The combined application of AG490 and DMTU produces a dose-dependent synergistic neuroprotective effect.
Yang
Qian-zi
QZ
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shanxi, China.
Lei
Chong
C
Lu
Zhi-hong
ZH
Wang
Bai-ren
BR
Xiong
Li-ze
LZ
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020032:Tyrphostins / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C038983:1,3-dimethylthiourea; D013890:Thiourea