ABSTRACT
Objective To investigate the protective effect of hypoxia-inducible factor-1α(HIF-1 α) on the neurovascular unit in rats with traumatic brain injury (TBI).Methods The fluid percussion model was applied to induce TBI in rats.A total of 600 rats were divided into sham operation group,TBI group,TBI + HIF-1 α silence group and TBI + control virus group according to the random number table,with 150 rats in each.Virus-mediated HIF-1 α silence gene and control virus were delivered 24 h before the fluid percussion injury.After 3,7 and 14 d,brain injury area and morphological changes in injured region were detected by HE staining,expressions of vascular endothelial cell markers (vWF) and HIF-1 α were detected by Western blot method,and expressions of vascular endothelial growth factor (VEGF),matrix metalloproteinase-9 (MMP-9),tumor necrosis factor-α (TNF-α),interleukin 6 (IL-6) and nuclear factor-κB (NF-κB) in peripheral blood and brain tissue were detected by ELISA method.Rat neural function was dynamically assessed using the modified neurological severity score (mNSS).Results (1) Brain injury area and edema area in TBI + HIF-1 α silence group were higher than those in TBI group at all time points (P ＜ 0.05).(2) Compared with sham operation group and TBI + control virus group,expression of HIF-1α in TBI group gradually increased and remained high at 7 and 14 d postinjury (P ＜ 0.05).Compared with TBI group,expression of vWF in TBI + HIF-1αsilence group decreased at all time points (P ＜ 0.05) and inhibited angiogenesis.(3) TBI + HIF-lα silence group versus TBI group showed remarkably decreased VEGF at all time points,increased expressions of TNF-α,IL-6 and NF-κB at all time point,and increased expression of MMP-9 at 7 and 14 d postinjury (all P ＜0.05).(4) TBI + HIF-1α silence group versus TBI group showed significant difference in mNSS at 7 and 14 d postinjury (all P ＜ 0.05).Conclusions After TBI,high expression of HIF-1αcan facilitate vascular formation and inhibit inflammatory reaction related factor expression,inducing the mitigation of brain edema and brain injury.Therefore,promoting HIF-1α expression may become a new means to improvement of neurovascular function after TBI.
ABSTRACT
Background Streptozotocin (STZ)-induced type 1 diabetic model is an acceptable model and is often used to the study of diabetic retinopathy (DR).However,the model is often established using retinal digest preparation in vitro in albino rats,and therefore it is difficult to evaluate the change of retinal vessels by fundus fluorescein angiography (FFA) in vivo.Recently,pigmented rats are being used as the DR model.But the study on the comparison between albino rat model and pigmented rat model is seldom.Objective This study was to observe and compare the manifestations of FFA and retinal digest preparation in early diabetic pigmented diabetic rat and albino diabetic rat,and to select the right model of DR using FFA.Methods Type 1 diabetic models were induced in 15 six-week-old health male BN rats and 15 six-week-old health male SD rats by the injection of STZ (55 mg/kg) via tail vein.The models were thought to be successful in the rats with the blood glucose level ≥ 16.7 mmol/L.The right eyes of the rats were extracted 6 weeks after injection of STZ.Lens were examined by slit lamp microscope.Retinal vascular changes were examined by fundus photography,FFA and periodic acid Schiff staining of retinal digest preparation.The manifestations of FFA and retinal digest preparation were contrasted between BN rats and SD rats.The number of eyes with lens opacification was compared by Chi-square test and the ratio of vascular endothelial cells and perithelial cells (E/P) was compared between BN rats and SD rats.The use and care of experimental animals complied the Statement of Ethic Committee of Tianjin Medicine University.Results Six weeks after injection of STZ,11 BN rats and 10SD rats were included in this study.The blood levels were (24.73±2.98) mmol/L and (22.36±3.65) mmol/L in BN rats and SD rats,respectively,without significant difference between the 2 types of rats (t =7.873,P＞0.05).Lens opacification occurred in 6 BN rats and in 5 SD rats (P=0.717).FFA showed the clear retinal vascular under the brown background.Evident vessel disorder and fluorescence leakage like background stage of DR were seen in 9 eyes.However,in the SD rats,retinal vessel abnormality could not exhibited owing to the interference of choroid fluorescent light from choroidal vessels and vortex vein.Retinal digest preparation exhibited that unevenness of vessel diameter,decrease of perithelial cells and increase of endothelial cells in both types of rats.The E/P values were 11.50±3.68in the BN rats and 12.86±3.94 in the SD rats,without significant difference between them (t=9.785,P＞0.05).Conclusions The abnormality of fundus vascular morphology can be better displayed in pigmented diabetic rats than albino rats by FFA in vivo.
ABSTRACT
Objective To study the effect of simvastatin (SIM) on the expression of neuron specific enoalse (NSE) in rat brain and serum after traumatic brain injury (TBI), and therapeutic effects of SIM on TBI thereof. Methods A total of 90 Sprague-Dwalye (SD) rats aged 8 weeks were randomly divided into sham TBI group, control group and treatment group (n=30). The TBI model was established in control group and treatment group by using Feeney method. Rats in treatment group were fed SIM 10 mg/kg in the evening pre-injury and in every evening post-injury while those in control group were fed the same dose of starch at the same time. Blood samples (3 mL) were collected from carotid atrery in three groups, then rats were sacrificed and brains were collected at different time points (3 h, 12 h, 24 h, 3 d, 7 d and 14 d post-injury). The serum ex-pressions of NSE were detected by ELISA method. The NSE expressions in hippocampal area CA3 were detected with immu-nohistochemistry. Results (1) In control group, the serum NSE level was significantly increased at 3 h after injury, reached the peak at 3 d, and was still higher than that of sham injury group at 14 d. In treatment group, the serum NSE level was in-creased 3 h after injury, reached the peak at 24 h, decreased after 3 d, and was near the sham injury group at 14 d after inju-ry, but was significantly lower than that of control group. (2) Immunohistochemical detection showed that the NSE optical density values in hippocampal area CA3 area were decreased at 3 h after injury in control group. The optical density values reached the lowest level between 3 d to 7 d and were still significantly lower than those of sham injury group at 14 d. In treat-ment group the optical density value was decreased at 3 h after injury, reached the lowest level between 12 h to 24 h and re-bounded significantly at 7 d, then at 14 d up to the level of sham injury group. Conclusion SIM can promote the decrease of serum NSE level in TBI rats and increase the NSE expression of hippocampal neurons of injured side, showing protective effects on neuronal damage after traumatic brain injury.