Effect of tumor necrosis factor receptor-1 on neurovascular regeneration after cerebral ischemia in mice / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of tumor necrosis factor receptor 1 (TNFR1) in angiogenesis and neurogenesis during cerebral ischemia in mice.Methods Twenty-four wild-type and 24 TNFR1 knockout mice were randomly divided into either a sham operation group or a focal cerebral ischemia group (n =12 in each group).5-bromodeoxyuridine (BrdU) was injected intraperitoneally at day 3 after cerebral ischemia and sham operation.At day 7 and 28 after cerebral ischemia,the double-label immunofluorescence staining of glucose transporter-1(Glut-1)/BrdU was used to evaluate the angiogenesis surrounding the areas of infarction.A labeled BrdU was used to detect the neural stem cell proliferation in the subventricular zone.Double-labeled doublecortin (DCX)/BrdU and neuronal nuclei antigen (NeuN)/BrdU were used to detect the migration and survival of neural stem cells,respectively.Results Under the normal condition,there was no significant difference in angiogenesis and the number of BrdU-positive cells in the subependymal zone (SVZ) between the wild-type (418.000 ± 28.404) and TNFR1 knockout (528.000 ± 60.597) mice (t =-1.644,P =0.131).At day 7 after cerebral ischemia,the number of Glut-1/BrdU-positive cells in the TNFR1 knockout mice was significantly less than that in the wild-type mice (14.833 ± 2.182 vs.27.5 ± 4.209) (t =2.672,P =0.023),and the number of DCX/B3rdU-positive cells was also significantly less than that in the wild-type mice (163.000 ± 11.106 vs.257.168 ± 12.213) (t =5.705,P =0.000).At day 28 after cerebral ischemia,the number of NeuN/BrdU-positive cells in the TNFR1 knockout mice was significantly less than that in the wildtype mice (6.000 ± 0.577 vs.11.000± 1.571) (t=2.988,P=0.014).Conclusions TNFR1 may play a promoting role in the neurovascular reggeneration in late cerebral ischemia.