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Objective To investigate the protective effect and its mechanism of DL-3-n-Butylphthalide on the brain damage in rats following whole brain irradiation.Methods A total of 120 male Sprague Dawley rats were randomly divided into sham-irradiation group,irradiatien group and DL-3-n-Butylphthalide group.The model of whole-brain irradiatien was established by exposuring rat brain to 4 MeV X-rays with a single-dose of 10 Gy.The rats were intraperitoneally injected with DL-3-n-Butylphthalide at the dosages of 0.3,1.0,and 3.0 mg/kg once a day.The contents of malondialdchyde and super oxide dismutase activity were measured,while the expressions of apoptosis-associated genes and the ultrastructural changes in hippocampus were examined by immunohistnchemisty staining and electron microscope,respectively.Results After irradiation,the content of malondialdehyde and the expression of apoptosis gene bax in rat brain tissue increased while the activity of super oxide dismutase(SOD) and the expression of anti-apoptosis gene bcl-2 decreased.Apoptosis was also observed in the neurons of hippocampus CA1.Compared with irradiation group,the content of malondialdehyde and the expression of bax gene in the DL-3-n-Butylphthalide group wen significantly reduced ( t =-3.89--1.96,2.72-3.48,P ＜ 0.05 ),while the activity of SOD and bcl-2 gene were significantly elevated ( t =2.94-3.76,-3.18--2.08,P ＜ 0.05),and the injury degree of neuron structure in the DL-3-n-Butylphthalide group was slighter than that in the irradiation group.Conclusions DL-3-n-Butylphthalide executes protective effects in a dose-dependent manner againest the radiation injury in rats brain by reducing the induction of malondialdehyde,raising the activity of SOD and inhibiting the generation of apoptosis.
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Alzhelmer's disease (AD) is an important neurodegenerative disease. Recent evidence has indicated that the production and loss of the myelin,sheath are associated with AD because the particular vulnerability of oligodendrocytes produced in the late stage makes the loss of the myelin sheath take a core position in the changes of the earliest stage of AD. The loss of the myelin sheath disrupts synchronization of impulses on which normal brain functions highly depend, and ultimately results in the function disruption of cortical association regions and subsequent neuronal loss. Meanwfiile, there are diverse mechanisms that make oligodendrocytes degeneration exist in the brains of AD. Therefore, elucidating its specific mechanism may help better understanding of AD, and thus provide some help for its treatment.
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Objective To study the effects of traumatic brain injury with or without hypotension on the development and severity of brain edema using the impact- acceleration model.Methods Brain tissue water content (BWC) was measured by the gravimetric technique in the cortex and striatum following traumatic brain injury (TBI) . The hypotension was induced by the combination of α - chloralose and pavulon after TBI.Results The mortality of this improved model of TBI was 48.6 %, but the rate of skull fracture was 6.4 %. Within the first 24 hours after TBI, the BWC of cortex and striatum in the survival rats showed a slight decrease at first, and then an increase. There appeared no difference in BWC between the two groups of TBI and the control. Nevertheless, the BWC in the area of parietal cortex at 24 hours after impact injury slightly increased by 0.5 % in comparison with that at 8 hours after impact [ (79.1 ± 0.5) % vs. (78.6 ± 0.5) %, P ＜ 0.05]. Meanwhile,the BWC of striatum didn't show the difference. However, while TBI was associated with hypotension, the BWC of both parietal cortex [ (81.5±0.9)% vs. (78.6±0.5)%, P＜0.001] and striatum [ (78.5±0.9)% vs. (75.5±0.9)%, P＜0.001) were significantly increased, by comparison with survival rats at 8 hours after impact. Moreover, the amplitude of increase in BWC achieved about 2.9 %.Conclusion The rats, suffering TBI without hypotension, presented the slight brain edema at the relatively late stage; by contrast, the rats,suffering from TBI with hypotension, had severe brain edema at the early stage.
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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.
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BACKGROUND: There are so many experimental and clinical researches on levels of nitrogen monoxide (NO) in serum and endothelins in plasma of patients with stroke; however, ratio and significance between them are still unclear.OBJECTIVE: To observe dynamic changes of levels of NO in serum and endothelins in plasma of patients with stroke.DESIGN: Case-controlled observation.SETTING: Neurological Department and Clinical Neurological Laboratory of the Second Hospital affiliated to Suzhou University.PARTICIPANTS: A total of 216 patients with acute cerebral infarction including 133 males and 83 females and 112 cases with cerebral hemorrhage including 68 males and 44 females were selected from Neurological Department of the Second Hospital affiliated to Suzhou University from September 1999 to December 2001. Another 106 subjects including 63males and 43 females were regarded as healthy control group.METHODS: Contents of NO in serum and endothelins in plasma were measured on 328 patients with stroke and 106 healthy subjects in the courses of 1-3 days, 1, 2, 4, 8 and 12 weeks with nitrate reductase and radio-immunity methods, respectively.MAIN OUTCOME MEASURES: Contents of NO in serum and endothelins in plasma; ratio between NO in serum and endothelins in plasma (NO/endothelins).RESULTS: ① As compared with those in the control group, content of NO in serum of patients with cerebral infarction and cerebral hemorrhage was decreased and reached the lowest value during acute period (within 1-3 days), and then increased gradually and closed to the normal level at about 4 weeks. In addition, content of endothelins in plasma was increased obviously during acute period, reached the peak at 2 weeks, and then decreased gradually. The level was still high at stage of recovery and closed to normal value within 4-8 weeks. ② As compared with that in the control group, NO/endothelins was decreased in cerebral infarction group at the courses of 1-3 days (P ＜ 0.05), reached the lowest value at 1 week (P ＜ 0.001), and increased to the normal level at 2 weeks. Moreover,NO/endothelins was remarkably decreased in cerebral hemorrhage group at the courses of 1-3 days (P ＜ 0.001), reached the lowest value at 1week (P ＜ 0.001), and increased gradually. The changes of course were great and the level reached above normal value at 8 weeks. There was significant difference of dynamic changes of NO/endothelins between cerebral hemorrhage group and cerebral infarction group (P ＜ 0.05).CONCLUSION: NO and endothelins play an important role in onset and development of ischemic cerebrovascular disease and hemorrhagic cerebrovascular disease, and their contents are related to prognosis.
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Objective To investigate the pattern of fluctuations and clinical significance of fasting serum insulin(FINS) and C-peptide(CP) levels in patients with different subtypes of acute cerebral infarct(ACI) and its relationship with serum lipid. Methods FINS and CP were measured in 152 ACI patients by chemiluminescent immunoassay. All ACI patients were classified into 5 major ischemic stroke subtypes according to the trial of org10172 in acute stroke treatment(TOAST) criteria. And then the relationship between FINS and CP level and serum lipid in different TOAST subtypes were analysed. Results The percentage of each ischemic stroke TOAST subtype was as follow: stroke of undetermined etiology 40.13%, small-vessel occlusion 34.21%, cardioembolism 5.26%, large-artery atherosclerosis 15.79%, and stroke of other determined etiology 4.61%. Among 5 major stroke subtypes, large-artery atherosclerosis patients had the highest levels of FINS and CP. The levels of FINS and CP in small-vessel occlusion were (8.237?5.144) ?U/ml and (1.761?0.975)ng/ml,respectively. Stroke of other determined etiology subtypes were associated with the lowest levels of FINS and CP. Apparently, other factors, such as TC, TG, LDL, SBP, DBP, age and HDL, could also affect the levels of FINS and CP in serum. Conlusions Levels of FINS and CP varied in different subtypes of ACI. There was a significant correlation among insulin resistance, hyperinsulinemia(HIS) and lipid metabolic abnormality in ACI.
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Objective To evaluate the value of 99m Tc-TRODAT-1 SPECT DAT imaging in the early diagnosing of Parkinsons disease (PD).Methods Eleven patients (9 PD and 2 possible PD) and eighteen healthy subjects matched by sex and age were studied with 99m Tc-TRODAT-1 SPECT DAT imaging. Striatum specific uptake of 99mTc-TRODAT-1 was calculated according to the ratio of DAT uptake in striatum (ST) and cerebellum (CB). Results In the hemi-Parkinsons disease group, the DAT specific uptake of 99mTc-TRODAT-1 was significantly lower (P＜0.01) in contralateral than in ipsilateral striatum to the clinically symptomatic side. There was significant decrease (p＜0.01) of striatum DAT uptake in patients with hemi-PD compared to the controls.Conclusions 99mTc-TRODAT-1 SPECT DAT imaging may help to confirm the diagnosis of PD at the early stage.
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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 CA1 and CA3 fields neuronal degeneration and necrosis,especially significant neuron loss was observed in the CA3 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.
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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.
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Objective To investigate the relationship between the neurotoxicity of A? and monoamine neurotransmissions in brain.Methods 32 male SD rats were divided into four groups: The model group, Nimodipine treatment group, Shenmai treatment group and the control group,there are 8 rats in each group.Under the stereotaxis A? was injected into NBM of rats to establish AD model, The extracellular monoamine neurotransmissions were detected by microdialysis in vivo with high performance liquid chromatography.Results The contents of frontal lobe NE,DA,5 HT in the model group were lower than those in the control group, which recovered to normal level,DA in hippocampus was higher than the control group;after the treatment of Shenmai,the result was similar to Nimodipine group.There was no difference between the two treatment groups.The rising levels of three kinds of transmitters in different brain area were different.Conclusion Neurotoxicity of A? might relate to dysfunction in monoamine system. A? on monamine system of inhibition was shown through multiple pathways, including the loss of Ca 2+ homeostasis.
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Objective To investigate the effects of aquaporin4 (AQP4) on the brain injury after cerebral ischemic reperfusion and to search the new method that can prevent and cure the injury. Methods Locally injection of naked DNA ( pcNDA3.1/Zeo), which carries AQP4 gene and reporter gene green fluorescent protein(GFP), in the brain was performed 12 h before ischemic challenge to up-regulate the AQP4 expression. The expressed level of AQP4, the infarction size and neurological deficit scores were estimated in three groups. Results (1) Exogenous AQP4 expression in the brain did not affect the healthy rat neurological deficit score; (2) Rat neurological deficit scores were 7.9?0.7, and 7.1?0.9 respectively in 12 h and 24 h after reperfusion in AQP4 injected group, which were lower than that in plasmid control group when both groups were challenged with reperfusion after ischemia; (3) Expression of AQP4 in the brain was higher in AQP4 injected group than plasmid control group and control group in early stage after reperfusion; (4) Expression of exogenous AQP4 in the brain increased the cortex and striatum infarction size 24 h after reperfusion, which were (261.0?18.2) mm 3 and (21.9?1.9) mm 3, respectively, in AQP4 injected group more than plasmid control group. Conclusions (1) Increased local AQP4 expression in brain does not affect neurological function in the healthy rat; (2) Pre-expression of AQP4 increase infarction size and neuro-functional injury; (3) Modification of AQP4 activity and regulation of AQP4 expression level would be the new strategy for the prevention of cerebral edema and the reduction of cerebral injury after stroke.
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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
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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
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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
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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
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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
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Objective To study the sequence of learning and memory loss in the rat after hemispheric irradiation. Methods After Sprague Dawly(SD) female rats were anaesthetized with chloral hydrate, their cerebral hemispheres were irradiated with a single dose of 5,15 or 30?Gy by 4?MeV electron. On D3,D7,D30 and D60, the learning and memorizing ability was measured with the Y maze test. Results On D3 and D7, the learning ability of SD rats was impaired most but partly restored in 1 to 2 months. In observation of memory loss, the intensity of cerebral function damage was in direct proportion to the increase of radiation dose.Conclusion The learning and memorizing ability of rats can be damage by hemispheric irradiation with the severity of impairment and possibility of recruitment depending on the dose.
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Objective To identify the radiation effect on different kinds of neurogliocytes in the hippocampus of rat brain and its dose, time relationship.Methods The brain sections were immunohistochemically stained separately with glial fibrillary acidic protein (GFAP), 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and CD11b(OX-42), to label the astrocytes, oligodendrocytes and microglial cells respectively. The number of GFAP, CNPase, and OX-42 positive cells in hippocampus were recorded and the data were analyzed by the Student's t test. Results By comparison with the unirradiated hemibrain, the relative number of GFAP and OX-42 positive cells increased in the hippocampus and the CNPase positive cells decreased in the irradiat hemibrain. The degree of change was both dose and time related and it was most significant at three months after 30?Gy irradiation. Conclusions The quantitative variation of different neurogliocytes in the hippocampus suggests that in addition to the decreasing traditional oligodendrocyte lineage, other increasing phenotypes, such as the astrocytes and microglial cells, as well as cellular interactions may also be involved in the pathogenetic process of brain radiation injury in the early stage.
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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
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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