P-glycoprotein is one of the members in the superfamily of ATP-binding cassette transporters. It is expressed in many sites in vivo, and is correlated with multidrug resistance. Under physiological conditions, as an efflux pump, P-glycoprotein in the blood-brain barrier can eliminate endogenous substrates and xenobiotics to maintain the balance of internal environment. But at the same time, it also limits the concentration of therapeutic drugs in brain, and thus reduces therapeutic efficacy. P-glycoprotein inhibitors can get drugs across the blood-brain barrier. It is of great importance to improve the blood concentration in brain and bioavailability of central nervous system drugs.

Objective To determine whether Topiramate(TPM) has an effect on basic fibroblast growth factor(bFGF) expression in hippocampus in a chronic kindling rat model of epilepsy.Methods Chronic kindling rat models were established by pentetrazole(PTZ) and divided into three groups:PTZ group,TPM group and normal control group.Each group then divided into three subgroups according to different time point of kindling(5,10 and 15 d).The expressions of bFGF in CA1,CA3 and dentate gyrus areas of hippocampus were detected by immunohistochemistry method.The cellular morphologic changes were observed by HE staining method.Results(1) There was no difference of epileptic praxiology between PTZ and TPM groups.(2) Compared with normal control group,bFGF-positive cells in dentate gyrus in PTZ group and TPM group were increased significantly at each time point(all P

Objective To explore the expression of Gamma-aminobutyric acid B recepter (GABABR) subunits mRNA and the effects of its agonist Baclofen in hippocampus after KA induced seizures,of experimental epileptic rats.Methods The GABABR subunits GAR1a及GAR2 mRNAs expression were determined in hippocampus of each experimental group after epileptic seizure and Baclofen interference by hybridization in situ. Results In early(6~12 h) time of KA induced epileptic rats, the mRNA levels of both receptor subunits in hippocampal formation were found downregulation widespreadly (all P

Objective To explore the expression of myelin transcription factor 1 (MyT1) and its significance in the brain of epileptic rats induced by lithium chloride-pilocarpine. Methods Models of epilepsy of SD rats were established by intraperitoneal injection with lithium chloride and pilocarpine. MyT1-positive cells in the cortex and hippocampal field CA 1 of epileptic rats were determined by immunofluorescence histochemistry.Results Compared with the control group, the number of MyT1-positive cells within the cortex and hippocampal field CA 1 of epileptic rats decreased significantly at 1 day after seizure ( P

Objective To investigate the protective effect of topiramate(TPM) on neuronal apoptosis in rats with acute seizures.Methods We treated the PTZ-induced seizure rats with TPM at 80mg/(kg?d)(high-dose group) and 40mg/(kg?d)(middle-dose group) or physiological saline(control group) for 2 weeks.Neuronal apoptosis in CA_1 and CA_3 regions in hippocampus was identified by terminal deoxynucletidyl transferase-mediated dUTP-biotin in situ nick end labeling(TUNEL) assay.Results Two weeks following seizures,TUNEL-positive neurons were detected in CA_1 and CA_3 regions each group.The numbers of TUNEL-positive neurons in CA_1 and CA_3 of control group were(35.83?)4.58 and(36.83?)3.83,(23.50?)2.81 and(25.50?)3.72 of high-dose TPM group,(31.52?)3.43 and(32.35?)4.69 of middle-dose TPM group.There was a very significant difference between high-dose TPM group and control group(all(P)0.05).Conclusion High dose administration of TPM after experimental status epilepticus may attenuate seizure-induced hippocampal neuronal injury.

Objective To study the effect of astrocyte-derived factors on the differentiation of neural stem cells from neonatal rats. Methods Neural stem cells from neonatal rats were isolated, cultured and expanded by neurosphere formation. Astrocytes were isolated and purified by a standard shaking method and the differential adhesion technique. With immunocytochemical labeling, the purity of astrocytes was determined by the expression of glial fibrillary acidic protein(GFAP). Astrocytes and neural stem cells were co-cultured without contact. Immunofluorescence examination was used to detect the effects of astrocyte-derived factors on the expression of neuron specific enolase (NSE), GFAP, and tyrosine hydroxylase(TH) of the differentiated cells. Results The purified astrocytes were 98% of GFAP positive. Co-culturing the neurospheres with astrocytes promoted more neural stem cells rapidly differentiationinto NSE positive cells( P

Objective To explore the protective effects of Acanthopanax senticousus saponins (ASS) on ischemia-hypoxia injury of cortical neuron. Methods The models of cortical neuron damage induced by hypoxia-ischemia (HI) and glutamate (Glu) were established on cultured embryonic cortical neurons. The neurons were randomly divided into HI group, Glu group, ASS group and control group. ASS (50 mg/L) was added into the ASS group before and during neuron damage. The rate of neuronal apoptosis was measured by flow cytometer, nitric oxide (NO) content was determined by Nitrate reductive assay and neuron survival was measured by MTT assay and the release of LDH. Morphologic change of neurons was observed under electron microscopy.Results (1) The cortical neuron survival decreased time-dependently in HI group and reached peak at 8h after hypoxia-ischemia. Glutamate leaded the cortical neuron survival decreasing time-dependently. (2) Compared with the control group, the cortical neuron survival decreased in HI group and Glu group, but the neuron apoptosis, the release of LDH and NO contents increased significantly (all P

Objective To investigate the protective effect of Edaravone on dopamine transporter in rat models of Parkinson disease.Methods Rat models of Parkinson disease were induced by injection 6-OHDA into right medial forebrain bundle. Edaravone at different doses (3.0 mg/kg, 1.0 mg/kg or 0.3 mg/kg) was injected intraperitoneally twice daily for two weeks. The same dose of normal saline was injected in the control group. One week after the treatment, the ?-radiation of rat bilateral striatum, cerebral cortex and cerebella cortex of each group was measured by a ?-counter and the brain tissue ID value was calculated.Results There was a significant difference of the radiation count in right striatum between the large dose group (0.47?0.06) ,medium doss group(0.37?0.02)and the control group (0.25?0.01)( P

Objective To explore a better method to establish temporal lobe epilepsy model by administrating drug in brain region.Methods Kainic acid(KA)4 ?g/kg was injected into rat's hippocampus by stereotactic operation.The rat's behavior,EEG and pathological changes were observed.Results After the rat's hippocampus injected with KA,staring,wet-dog shakes,masticatory movement and clonus of limbs occurred successively.The seizures were paroxysmal with rotation,unsettled state of jump and tic of limbs.The rats' behavior gradually recovered to normal after 10 hours.Then the spontaneous seizure(mostly rating 2～4)occurred 1～3 times every week.Cluster electric discharge,spike waves and sharp waves were recorded in cerebral cortex.KA-treated rats could result in hippocampal CA1 and CA3 fields neuronal degeneration and necrosis,especially significant neuron loss was observed in the CA3 field of KA injected ipsilateral side.Conclusions Injection KA in brain region of rat can establish temporal epilepsy model.The symptom,electrophysiology and pathological changes of temporal lobe epilepsy in the rat model are almost the same as those in human being.The KA induced rat model is an ideal tool to research human temporal lobe epilepsy.

Objective To examine the effect of treatment with reduced glutathione(GSH) in 6-OHDA induced rat models of Parkinson's disease(PD).Methods 35 SD rats were received injection of 6-OHDA by medial forebrain bundle to make lateral PD models.According to rotation test induced by Apomorphine 6 weeks later,the model rats were divided into partial PD group and total PD group.Each group was further divided into reduced glutathione hormone(GSH) sub-group and control sub-group randomly.The sub-groups were treated intraperitoneally with GSH or normai saline every day for 4 weeks,respectively.The functional outcome of each group was measured using the Apomorphine induced rotation test at 2,4,6 and 8 weeks after treatment.Results Successful PD models were made in 27 of 35 rats,which included 13 partial PD models and 14 total PD models.The numbers of rotation per minute induced by Apomorphine at 4,6 and 8 weeks after treatment with GSH in partial PD group were significantly lower than that before treatment and in the control sub-group((P