The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.
The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia.
Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.|Department of Neurology, The Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, Jiangsu, China.|Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Qingxiu
Q
Zhang
Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Hongyu
H
Cheng
Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Rong
R
Rong
Department of Neurosurgery, Xuzhou First People's Hospital, Xuzhou, 221002, Jiangsu, China.
Hui
H
Yang
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Qiuhong
Q
Ji
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221000, Jiangsu, China.
Qingjie
Q
Li
Department of Neurology, The Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, Jiangsu, China.
Liangqun
L
Rong
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, Jiangsu, China. ghu@njmu.edu.cn.
Gang
G
Hu
Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. dryunxu@163.com.
Yun
Y
Xu
D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases / Q000172:deficiency* / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D008565:Membrane Proteins; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C501445:Dlg2 protein, mouse; D051528:Guanylate Kinases
Excitotoxicity; Inflammatory cytokines; Ischemic brain damage; PSD-93