OBJECTIVETo investigate whether tri-ortho-cresyl phosphate (TOCP) and organophosphate compound that could produce organophosphate-induced delayed neuropathy (OPIDN) in hen and other sensitive species, directly affect oligodendrocytes, the myelin-forming cell of the central nervous system.

METHODSThis was achieved by a combination of measurements of cell viability (MTT) cell pathological observation in the presence and absence of the compound cultured hen brain oligodendrocytes were prepared and treated with various concentrations of TOCP.

RESULTSIn a time-course experiment TOCP showed a cytotoxic effect to oligodendrocytes and led to the oligodendrocyte processes disintegrated and membranous blebs, cytoplasmic vacuolation following exposure time of 24 h or longer, it showed a dose-depended and time-depended manner cytotoxic effect to oligodendrocytes at dose levels of 0.5 approximately 1.5 microg/ml (1.35 approximately 4.05 mol/L) concentrations of TOCP for 24 - 72 h exposure. MTT experiment indicated that TOCP inhibited cell viability by dose-depended manner at dose levels of 0.5 approximately 1.5 microg/ml (1.35 approximately 4.05 mol/L) concentrations of TOCP for an 24 h exposure.

CONCLUSIONSTOCP is cytotoxic to oligodendrocytes and leads to the oligodendrocyte processes disintegrated and membranous blebs, vacuolar degeneration, which suggests that this oligodendrocyte degeneration may involve in the pathogenesis mechanism for OPIDN.

Animals ; Cell Survival ; Cells, Cultured ; Cerebral Cortex ; pathology ; Chickens ; Dose-Response Relationship, Drug ; Oligodendroglia ; drug effects ; pathology ; Tritolyl Phosphates ; toxicity ; Vacuoles ; drug effects ; pathology

OBJECTIVETo observe the effect of different doses of acetamide on the histopathology in the cerebral cortex of rats with tetramine (TET) poisoning and to provide a basis for the treatment of fluoroacetamide poisoning with acetamide.

METHODSEighty clean Sprague-Dawley rats were randomly divided into five groups: saline control group,dimethylsulfoxide water solution control group,TET poisoning group, acetamide (2.88 g/kg/d) treatment group, and acetamide (5.68 g/kg/d) treatment group, with 16 rats in each group. Rats in the poisoning group and treatment groups were poisoned with TET by intragastric administration after fasting; then, saline was injected intramuscularly into rats of the poisoning group, and different doses of acetamide were injected intramuscularly into rats of treatment groups; the course of treatment was 5 d. At 3 h, 12 h, 48 h, and 7 d after treatment, the cerebral cortex was harvested from rats in each group, and the histopathological changes in the cerebral cortex were evaluated under light and electron microscopes.

RESULTSThe light microscopy showed that the TET poisoning group had hypoxia changes in the cerebral cortex, which worsened over time; the treatment groups had reduced hypoxia changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group. The electron microscopy showed that the apoptosis of neuronal cells were the main pathological changes in the TET poisoning group; the treatment groups had reduced apoptotic changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group.

CONCLUSIONNo pathological changes associated with the synergistic toxic effect of acetamide and TET are found in the cerebral cortex. Acetamide (2.88 g/kg/d) could reduce central nervous lesions, but the efficacy is not improved after increasing the dose. For patients who cannot be identified with TET or fluoroacetamide poisoning, acetamide could be considered for treatment.

Acetamides ; pharmacology ; Animals ; Bridged-Ring Compounds ; toxicity ; Cerebral Cortex ; drug effects ; pathology ; Disease Models, Animal ; Male ; Rats ; Rats, Sprague-Dawley

AIMTo determine the protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats.

METHODSSlow microinjection of endothelin-1 (120 pmol in 6 microL, for > 6 min) into the region near the middle cerebral artery was used to induce focal cerebral ischemia. ONO-1078 (0.1 mg.kg-1) was i.p. injected 1 h before endothelin-1 injection. Neurological symptoms, brain edema, brain infarction size, and the survival neurons in cortex and striatum were observed 24 h after ischemia.

RESULTSIntracerebral microinjection of endothelin-1 induced remarkable neurological symptoms, brain infarction, brain edema, and decrease of survival neurons in the cortex and striatum. In rats pretreated with ONO-1078, endothelin-1-induced brain edema and brain infarction size were decreased. The numbers of survival neurons in striatum and cortex were increased significantly. The neurological symptoms were improved but not significantly.

CONCLUSIONONO-1078 possesses neuroprotective effect against cerebral ischemic injury induced by endothelin-1, therefore, leukotrienes may play a role in the injury of cerebral ischemia.

Animals ; Behavior, Animal ; drug effects ; Brain Edema ; pathology ; Brain Ischemia ; chemically induced ; pathology ; Cerebral Cortex ; pathology ; Cerebral Infarction ; pathology ; Chromones ; pharmacology ; Corpus Striatum ; pathology ; Endothelin-1 ; Leukotriene Antagonists ; pharmacology ; Male ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

The involvement of apoptosis in mitochondrial toxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3-NPA at a dose of 20 mg/kg or vehicle control was intraperitoneally into the rats. Three days later, rats were exposed to 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes were assessed by 2,3,5-triphenyltetrazolinm chloride (TTC) staining 24 h after reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as compared to the vehicle-treated group, pretreatment with 3-NPA could reduce the infarct volume by 23.3% and decrease the number of TUNEL-positive neural cells and apoptotic percentage by 47% (P<0.05) and 44.9% (P<0.01), respectively. It was concluded that the development of 3-NPA-induced ischemic tolerance in brain might be related to the decreases in neural cell apoptosis.
Animals ; Apoptosis ; drug effects ; Cerebral Cortex ; blood supply ; Cerebrovascular Circulation ; DNA Damage ; Infarction, Middle Cerebral Artery ; pathology ; Ischemic Attack, Transient ; chemically induced ; pathology ; Ischemic Preconditioning ; Male ; Middle Cerebral Artery ; pathology ; Nitro Compounds ; Propionates ; Rats ; Reperfusion Injury ; pathology

OBJECTIVE: To investigate whether heroin can directly induce apoptosis in primary cultured cortical neurons of rat's brain. METHODS: Cultured primary neurons cultures were obtained from cerebral cortex of embryo rats. After 7 days, the cells were incubated with different concentrations of heroin (purity-80%) for 24 hours. The neuronal survival was assessed by cell viability counting with fluorescent diacetate (FDA) staining. The morphological and biochemical changes were observed with Hoechst 33258 fluorescent staining and then analyzed by agarose gel electrophoresis, respectively. RESULTS: After treatment with different concentrations of heroin, the neurons showed a decreased survival rate in a dose dependent manner, and there was a significant difference in the survival rate between the heroin group and the control group (P < 0.05). When exposed to different concentrations of heroin, neurons exhibited the morphological and biochemical features of apoptosis, including cell shrinkage, neurite degeneration, network disappearance, condensation and aggregation of nuclear chromatin, and the formation of DNA ladders. With the increase of heroin concentration of rat's brain more apoptotic bodies were seen. CONCLUSION Heroin can directly induce apoptosis in primary cultured cortical neurons in rat's brain.
Animals ; Apoptosis/drug effects* ; Cell Nucleus/pathology* ; Cell Survival/drug effects* ; Cells, Cultured ; Cerebral Cortex/pathology* ; DNA Fragmentation/drug effects* ; Dose-Response Relationship, Drug ; Electrophoresis, Agar Gel/methods* ; Female ; Heroin/pharmacology* ; Male ; Neurons/pathology* ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling

OBJECTIVETo study the protection of puerarin on the cerebral injury in the rats with acute local ischemia.

METHODRat was evaluated model of acute local cerebral ischemia was made by ligating middle cerebral artery. The cerebral damage toxylin and eosin((HE).

RESULTThe number of died neurons were significantly less in puerarin-treated rats than in the rats with cerebral ischemia (P < 0. 05). Similarly, the cerebral edema were significantly attenuated in the puerarin-treated rats as compared with cerebrally ischemic rats.

CONCLUSIONPuerarin can prevent the neuron from damage induced by acute cerebral ischemia.

Animals ; Brain Ischemia ; pathology ; Cell Death ; drug effects ; Cerebral Cortex ; pathology ; Female ; Infarction, Middle Cerebral Artery ; pathology ; Isoflavones ; pharmacology ; Male ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Wistar ; Vasodilator Agents ; pharmacology

OBJECTIVETo study the effects of deltamethrin on intracellular free Ca2+ concentration and apoptosis in rat neural cells.

METHODSWister rats were randomly divided into 4 groups(3 treated groups and 1 control). Intracellular free Ca2+ concentration in rat neural cells was measured by using the fluorescent Ca2+ indicator Fura-2/AM. Apopotic rate of neural cells was measured by using FACS420 Flow Cytometer.

RESULTSIntracellular free Ca2+ concentration at 5 h after deltamethrin exposure [hippocampus: (389.94 +/- 43.64) nmol/L, cerebral cortex: (449.33 +/- 23.23) nmol/L], at 24 h[hippocampus: (340.47 +/- 32.36) nmol/L, cerebral cortex: (311.62 +/- 25.48) nmol/L] and at 48 h[hippocampus: (287.13 +/- 24.29) nmol/L, cerebral cortex: (346.55 +/- 36.87) nmol/L] were all higher than those of the control group[hippocampus: (203.24 +/- 18.53) nmol/L, cerebral cortex: (226.85 +/- 14.81) nmol/L, P < 0.01]; Apoptotic rate in neural cells 24 h and 48 h later [hippocampus: (8.45 +/- 1.02)%, (9.44 +/- 1.14)%, cerebral cortex: (7.90 +/- 0.49)%, (8.01 +/- 0.87)%] were also higher than those of the control group[hippocampus: (2.97 +/- 0.36)%, cerebral cortex: (3.50 +/- 0.48)%, P < 0.01)] and increased with time prolonged.

CONCLUSIONExposure to high dose of deltamethrin would interfere with intracellular free Ca2+ concentration and apoptotic rate in rat neural cells, suggesting that there may be certain relation between them.

Animals ; Apoptosis ; drug effects ; Calcium ; metabolism ; Cerebral Cortex ; drug effects ; metabolism ; pathology ; Flow Cytometry ; Hippocampus ; drug effects ; metabolism ; pathology ; Insecticides ; toxicity ; Neurons ; cytology ; drug effects ; metabolism ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar

This study is to investigate the modulation of Kudiezi (KDZ) injection on differential protein expression in cerebral cortex of rats with cerebral ischemic stroke and heat toxin syndrome established by intraperitoneal injection of carrageenan and middle cerebral artery occlusion (MCAO) methods. According to random number table rats were divided into three groups: drug group, model group and sham group. The tripheye tetrazolium chloride (TTC) staining and HE staining were used to observe brain tissue injury of rats. After therapeutic intervention with above drug for seventy-two hours, the level of differential protein expression was analyzed by two-dimensional gel electrophoresis (2-DE). The results show that there are differential protein expressions between cerebral ischemic stroke and heat toxin syndrome rats and sham rats. Furthermore, as a Chinese medicine injection with effect of clearing heat, resolving toxin and dredging collaterals, KDZ injection can decrease alleviate morphological changes of cerebral ischemia, regulate the levels of some differential proteins expression.
Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; pathology ; Cerebral Cortex ; drug effects ; metabolism ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression ; drug effects ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Stroke ; drug therapy ; genetics ; metabolism ; pathology

OBJECTIVETo study the effect of deltamethrin on the apoptotic rate and the expression of caspase-3 in rat neural cells.

METHODSMale Wistar rats were randomly divided into 5 groups: control, 5 h, 24 h, 48 h and 5 d exposed groups. Apoptotic rate and the expression of caspase-3 were measured by FACS420 Flow Cytometer; Ac-DEVD-pNa was used as a substrate to detect the activity of caspase-3.

RESULTSApoptotic rates in 24 h, 48 h and 5 d exposed groups in hippocampus and cerebral cortex [hippocampus: (8.45 +/- 1.02)%, (9.44 +/- 1.14)%, (7.58 +/- 0.75)%; cerebral cortex: (7.90 +/- 0.49)%, (8.01 +/- 0.87)%, (7.97 +/- 0.41)% respectively] were higher than those in the control [hippocampus: (2.97 +/- 0.36)%; cerebral cortex: (3.50 +/- 0.48)%] (P < 0.01); the activity of caspase-3 in 5 h, 24 h and 48 h exposed groups (A(405) nm in hippocampus: 0.389 +/- 0.038, 0.472 +/- 0.041, 0.295 +/- 0.049; A(405) nm in cerebral cortex: 0.321 +/- 0.068, 0.429 +/- 0.077, 0.344 +/- 0.047) and 5 d group of hippocampus (0.246 +/- 0.065) were all higher than those of the control (hippocampus: 0.184 +/- 0.054; cerebral cortex: 0.198 +/- 0.049) (P < 0.05, P < 0.01); the expression of caspase-3 in 5 h, 24 h and 48 h exposed groups increased apparently while 5 d group did not.

CONCLUSIONExposure to high dose of deltamethrin would affect the apoptosis, the activity and expression of caspase-3 in rat neural cells. The increase in caspase-3 activity and expression occurred before the rising of neuronal apoptotic rate may be the upstream event of apoptosis.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; Caspases ; metabolism ; Cerebral Cortex ; enzymology ; pathology ; Hippocampus ; enzymology ; pathology ; Insecticides ; pharmacology ; Male ; Nitriles ; pharmacology ; Pyrethrins ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar

This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.
Animals ; Benzofurans ; isolation & purification ; pharmacology ; Cell Count ; Cerebral Cortex ; pathology ; Cerebral Ventricles ; pathology ; Dentate Gyrus ; pathology ; Hippocampus ; pathology ; Infarction, Middle Cerebral Artery ; complications ; Male ; Motor Activity ; drug effects ; Neurogenesis ; drug effects ; Neurons ; drug effects ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; pathology ; physiopathology ; Salvia miltiorrhiza ; chemistry