ABSTRACT
Objective To investigate and analyze the behavioral and pathological differences in early-stage mouse models of epilepsy established by 2 different administration routes for kainic acid(KA),intracerebroventricular(ICV)injection and intraperitoneal(IP)injection.Methods A total of 100 male C57BL/6N wild-type(WT)mice(20～22 g)were randomly divided into ICV+normal saline(NS)control group(n=10),ICV+KA model group(n=40),IP+NS control group(n=10)and IP+KA model group(n=40).The ICV+KA model group was given 600 nL of KA(0.5 mg/mL)via ICV injection,and the IP+KA model group was injected with different dose of KA(25 mg/kg).Two control groups were administered equal volumes of NS via corresponding routes.After 3 d of modeling,the evaluation of behavioristics,molecular biology(including Western blotting),and neuropathological assessments(including FJB staining,TUNEL staining and immunofluorescence staining)were performed.Results No epileptic seizures were observed in both 2 control groups,while exhibited seizures were observed in both model groups.The mortality rates of the IP+KA group and the ICV+KA group were 47.50%and 65.00%respectively,while the success rates of modeling were 80.00%and 60.00%respectively.Compared with the IP+KA group,the ICV+KA group showed a significant increase in success rate and a significant reduction in mortality rate.FJB and TUNEL staining results showed that,compared with the IP+KA group,the severity of neurodegeneration and apoptotic changes in the hippocampus of the ICV+KA group were more significant(P＜0.05).Compared with the IP+KA group,there was also a significant difference in the expression of apoptotic proteins in the hippocampus of the ICV+KA group(P＜0.05).Immunofluorescence results showed that the astrocytes and microglia in the hippocampus and cortex of the ICV+KA and IP+KA groups were significantly activated compared with the control groups(P＜0.05),but the activation of glial cells in the hippocampus and cortex of the ICV+KA group was stronger than that of the IP+KA model group(P＜0.05)and the activation levels in the ICV+KA group were higher than in the IP+KA model group(P＜0.01).Moreover,expression levels of GFAP and Iba-1 proteins in the hippocampus and cortex were higher in the ICV+KA group than the IP+KA group(P＜0.05).Conclusion Two routes of KA administration are effective in construct epilepsy models.The mice with ICV administration route show a higher success rate and lower mortality rate,and more significant neuropathological damage and glial cell activation.
ABSTRACT
Objective:To explore the neural mechanism of language dysfunction in patients with subacute stroke using functional near-infrared spectroscopy (fNIRS).Methods:Sixteen patients with non-fluent aphasia after subacute stroke (aphasia group), 16 patients with non-aphasia after stroke (non-aphasia group), and 16 healthy middle-aged and elderly subjects (control group) were enrolled into our study. The 6-min resting-state data of fNIRS were collected. Four language-related regions, Broca area, Wernicke area, dorso lateral prefrontal cortex (DLPFC), and supplementary motor area (SMA), were selected as regions of interest (ROIs), and the whole brain functional connection strength and functional connection strength in ROIs and between each two ROIs were analyzed by NirSpark software.Results:Compared with the control group (0.53±0.15) and non-aphasia group (0.47±0.12), the aphasia group had significantly decreased whole brain functional connection strength (0.29±0.14, P<0.05). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the left Wernicke area, right Wernicke area, left Broca area, left SMA area, right SMA area and left DLPFC area ( P<0.05, FDR). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the right Wernicke-left Wernicke area, right Wernicke-right Broca area, right Wernicke-left Broca area, right Wernicke-right DLPFC area, right Wernicke-left DLPFC area, right Wernicke-right SMA area, right Wernicke-left SMA area, left Wernicke-right Broca area, left Wernicke-left Broca area, left Wernicke-right DLPFC area, left Wernicke-left DLPFC, left Wernicke-right SMA area, left Wernicke-left SMA area, right Broca-left Broca area, right Broca-left DLPFC area, right Broca-right SMA area, right Broca-left SMA area, left Broca-right DLPFC area, left Broca-left DLPFC area, left Broca-right SMA area, left Broca-left SMA area, right DLPFC-left DLPFC area, right DLPFC-right SMA area, right DLPFC-left SMA area, left DLPFC-right SMA area, left DLPFC-left SMA area, and right SMA-left SMA area ( P<0.05, FDR). Conclusion:Abnormal functional connectivity strength of the whole brain and language-related key brain areas might be the neural mechanism of language dysfunction in patients with non-fluent aphasia after subacute stroke.
ABSTRACT
OBJECTIVE To determine the pharmacokinetic parameters of perlolyrine in rats.METHODS The plasma concentration and pharmacokinetic parameters of perlolyrine were determined by means of GC-MS with selected ion (m/z 247 and m/z 248) and ［2-15N］perlolyrine(m/z 248) as the internal standard.RESULTS The concentration-time profile of perlolyrine after oral administration of perlolyrine fitted a two-compartment open model.The pharmacokinetic parameters were t1/2α=0.31 h, t1/2β=4.62 h, t1/2ka=0.10 h, tmax=0.34 h, cmax=18.74 ng.mL-1,K12=0.82 h-1, K21=0.38h-1,K10=0.29 h-1,Vb=108.16 L.kg-1,AUC=98.54 ng.h.mL-1,respectively.CONCLUSION The method is constant,sensitive and accurate.It provided a scientific basis for the clinical use of perlolyrine.
ABSTRACT
Experimental research showed that Gan Tang Zhi can influence blood clotting and plasma fibrinolytic system of rabbits, 15min after introvenous injecting 6.25mg/kg or 25mg/kg Gan Tang Zhi into rabbit it can pronouncedly prolong prothrombin time ( PT ) , thrombin time ( TT ) , and kaolin partial thromboplastin time ( KPTT ) ; and cause remarkable increase of fibrin degradation product ( FDP ) , Gan Tang Zhi can also shorten englobulin lysis time (ELT) and decrease fibri-nogen.
ABSTRACT
TMP. The results suggested that 12D-TMP and 6D-TMP possessed remarkable isotope effects, and that the pyrazine ring of TMP may be responsible for its pharmacodynamics, while the substituted groups might primarily govern its pharma-cokinetics and toxicity. The results also indicated that to study the structure activity relationship of TMP and to modify its chemical structure are very fruitful for the development of TMP analogues of high potency.
ABSTRACT
The influences of propylene glycol mannate sulfate (PGMS) on experimental thrombosis and thrombolysis in vivo were studies after iv 8. 125, 6. 25, 12. 5 , 25mg/Kg in rabbits, and the effect of antithrombosis of PGMS was compared with that of heparin. The results showed that PGMS possessed remarkable effect of antithrombosis. In order to explore the mechanism of antithrombosis of PGMS, we studied the influences on the fibrinolytic and coagulant function of rabbits. The results showed that PGMS can pronouncedly prolong the prothrombin time (PT), thrombin time (TT), kaolin partial thromboplastin time (KPTT), and enhance the activity of antithrombin-III (AT -III). PGMS can cause a remarkable increase in fibrin degradation product (FDP) , shorten euglobulin lysis time (ELT) , and a decrease in the contents of fibrinogen and plasminogen activity. These results suggested that PGMS probably exert the antithrombotic effect by inhibiting coagulation and activating fibrinolysis.