ABSTRACT
Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.
ABSTRACT
OBJECTIVE:To study the effects of tilianin(TIL)on brain tissue in rats with cerebral ischemia-reperfusion injury. METHODS:Totally 120 male SD rats were randomly divided into sham operation group(0.9% sodium chloride solution),model group(0.9% sodium chloride solution),nimodipine group(32 mg/kg)and TIL low-dose and medium-dose,high-dose groups(4, 8,16 mg/kg),with 20 rats in each group. The rats were given relevant medicine intragastrically,once a day,for consecutive 7 d. 15 min after last medication,cerebral ischemia-reperfusion injury model was established by reforming suture-occluded method. The neurological deficit score in rats were evaluated, and percentage of cerebral infarction volume of rats was determined. Histopathological changes of brain tissue were observed by HE staining. The activities of SOD,CAT and LDH,MDA content in cerebral tissue of rats were determined. The expression of calcitonin gene-related peptide(CGRP)and peripheral vascular endothelial growth factor receptor 2 (VEGFR2) protein were determined by Western blot assay. RESULTS:Compared with sham operation group,neurological deficit score and percentage of cerebral infarction volume of model group were increased significantly(P＜0.01);the nerve cells in brain tissue were significantly reduced and the interstitial edema was obvious. SOD and CAT activities were decreased significantly,LDH activity was increased significantly,MDA content was decreased significantly,protein expression of CGRP and VEGFR2were increased significantly(P＜0.05 or P＜0.01). Compared with model group,neurological deficit score of nimodipine group,TIL medium-dose and high-dose groups were decreased significantly;percentage of cerebral infarction volume was decreased significantly (P＜0.05 or P＜0.01);above pathological conditions of cerebral tissue in rats were relieved significantly;SOD and CAT activities were strengthened significantly,MDA content and LDH activities were decreased significantly,protein expression of CGRP and VEGFR2were increased significantly (P＜0.05 or P＜0.01). CONCLUSIONS: TIL has certain protective effects on cerebral ischemia-reperfusion injury model rats,and its mechanism may be related to the up-regulation of CGRP and VEGFR2expression.
ABSTRACT
In order to research and enhance bioavailability of chlorogenic acid and rutin[CA-R] via the oral route, chitosan coated composite phospholipid liposomes [C-CPLs] were applied to study on preparation, permeability and pharmacokinetic of C-CA-R-CPLs. TheC-CA-R-CPLs were prepared by the method of ethanol injection. The entrapment efficiency [EE], average particle sizes, polymer disperse index [PDI], zeta potential, shape and in vitro drug release were investigated to characterize physicochemical parameters of C-CA-R-CPLs. The penetration properties from C-CA-R-CPLs were studied through Caco-2 cells model and the pharmacokinetics in Sprague-Dawley [SD] rats were evaluated by rat jugular vein intubation tube. The EE of C-CA-R-CPLs of CA and R was 91.3+/-2.13% and 92.6+/-2.44%, particle size of C-CA-R-CPLs was 176.7+/-2.3 nm, PDI was 0.207+/-0.014 and zeta potential of 12.61+/-1.33 mV. CA-RCPLs and C-CA-R-CPLs were spherical or elliptical sphere and the bilayer of the CPL was observed obviously under transmission electron. The C [max], t1/2 and AUC[0-12] h values of CA and R for groups of C-CA-R-CPLs were significantly increased.In conclusion, TheC-CA-R-CPLs as a novel nano-formulation have potential to be used to enhance the oral bioavailability of poorlywater-soluble drugs after oral administration