Animals ; Apoptosis ; drug effects ; Brain Ischemia ; pathology ; Hippocampus ; cytology ; drug effects ; pathology ; Neurons ; drug effects ; pathology ; Rats ; Rats, Wistar ; Reperfusion Injury ; pathology ; Sulfinic Acids ; pharmacology

The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 microg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 microg/(kg.h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-alpha was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-alpha and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities.
Animals ; Brain ; drug effects ; pathology ; Brain Ischemia ; drug therapy ; pathology ; Fibroblast Growth Factor 2 ; administration & dosage ; Infusions, Intravenous ; Rabbits ; Reperfusion Injury ; drug therapy ; pathology ; Treatment Outcome

OBJECTIVETo investigate the toxicity of intragastrically administered N, N-dimethylformamide (DMF) in female Wistar rats, and to provide experimental data for the overall evaluation of DMF toxicity under different ways of exposure.

METHODSForty female Wistar rats weighing 150∼180 g were randomly divided into four groups: control group (treated with water) and three DMF exposure groups with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. After oral administration of DMF once a day for 14 consecutive days, the rats were weighed and sacrificed. The liver, kidney, brain, and uterus were weighed to calculate organ indices. The pathological changes in the liver were examined by HE staining. The protein expression of HSP70 in the liver, kidney, and brain was determined. Finally, peripheral lymphocytes were collected from the arteria cruralis to determine DNA damage by comet assay.

RESULTSFourteen days after DMF exposure, the body weight and organ indices of the kidney, brain, and uterus showed no significant changes. However, the liver index showed concentration-dependent increase in all DMF exposed groups (3.52±0.21, 3.55±0.13, and 3.88±0.22 in the low-, medium-, and high-dose groups, respectively), as compared with the control group (3.24±0.28) (P < 0.05 or P < 0.01). The pathological damage in the liver also showed a concentration-dependent manner. Inflammatory cell infiltration and granular degeneration in centrilobular hepatocytes were observed in the high-dose group. No significant change in protein expression of HSP70 was observed in the liver, kidney, or brain of DMF-exposed rats (P > 0.05). DNA damage was induced by DMF, and the DNA percentage of lymphocyte comet tail, average tail length, and tail moment in exposed groups were all significantly increased as compared with the control group (P < 0.05 or P < 0.01).

CONCLUSIONGavaged DMF can induce liver injury and DNA damage in lymphocytes in rats 14 days after administration. There is no significant change in protein expression of HSP70 in the liver, brain, or kidney after DMF exposure.

Animals ; Brain ; drug effects ; pathology ; DNA Damage ; drug effects ; Dimethylformamide ; toxicity ; Female ; Gastric Lavage ; HSP70 Heat-Shock Proteins ; metabolism ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lymphocytes ; drug effects ; Rats ; Rats, Wistar ; Toxicity Tests

OBJECTIVETo evaluate the role of water channel AQP4 in NMDA-induced brain injury in mice.

METHODSIn AQP4 gene knockout (AQP4(-/-)) mice, brain injury was induced by microinjection of NMDA into the cortex. The injured area was determined by toluidine blue staining, degenerated neurons were detected by Fluro-Jade B staining, and increased blood-brain barrier (BBB) permeability was evaluated by IgG immunostaining.

RESULTCompared with wild-type mice, AQP4(-/-) mice exhibited increased cortical lesion area, aggravated neuron degeneration, and increased BBB disruption after NMDA microinjection.

CONCLUSIONAQP4 may play a protective role in NMDA-induced brain injury in mice.

Animals ; Aquaporin 4 ; genetics ; physiology ; Blood-Brain Barrier ; pathology ; Brain ; drug effects ; pathology ; Mice ; Mice, Knockout ; N-Methylaspartate ; toxicity

OBJECTIVEThe investigated the effects of Dengzhan Xixin on brain water content, blood-brain barrier (BBB) permeability, T2-weighted imaging (T2WI), metabolites and the lesion ratio after cerebral ischemia-reperfusion injuries (IRI).

METHODThe 65 rats were randomly individed into three groups, the sham-operated group, the ischemia-reperfusion group and the Dengzhan Xixin treatment group. The models of ischemia-reperfusion of middle cerebral artery in rats were established by placing an intraluminal suture. The Dengzhan Xixin treatment group were injected 10% Dengzhan Xixin injection 22.5 mg kg(-1) after ischemia 1.5 h. The sh am-operated group (n=5) were sacrificed on 1 to measure brain water content and BBB permeability. The rats of the ischemia-reperfusion group (n=30) and the Dengzhan Xixin treatment group (n=30) were sacrificed at reperfusion for 6 h, 12 h, 1 d, 2 d, 4 d, 7 d, respectively, after ischemia 1.5 h. The additional 35 rats were individed into the same three groups. The changes of T2WI and metabolites in the brain were observed, and rats were sacrificed at reperfusion for 1 d, 2 d, 4 d after ischemia 1.5 h to determine the lesion ratio by TTC.

RESULTIn the ischemia-reperfusion group, brain water content(77.93+/-0.68)% and BBB permeability (3.77+/-0.28) increased after reperfusion for 6 h. The peak time of brain water content was at 4 d (83.82+/-0.49)% and BBB permeability was at 2 d (5.51+/-0.24)%. In the ischemia-reperfusion group and the Dengzhan Xixin treatment group, there were hyperintense signals in the injury region of T2WI. In the ischemia-reperfusion group after reperfusion for 1 d, the ratio of NAA/Cr decreased and Cho/Cr increased. In the Dengzhan Xixin treatment group, the ratio of NAA/Cr increased and Cho/Cr decreased. In the treatment group, the lesion ratio decreased by TTC was 16.78+/-1.45 and in the ischemia-reperfusion group was 21.27+/-1.73 at 2 d.

CONCLUSIONDengzhan Xixin may relieve cerebral ischemia-reperfusion injury by influencing the metabolites of brain, stabilizing BBB and decreasing brain edema.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Ischemia ; complications ; metabolism ; pathology ; Flavonoids ; pharmacology ; Male ; Permeability ; drug effects ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; metabolism ; pathology ; Water ; metabolism

OBJECTIVETo investigate the protective effect of cilostazol administrated intranasally on chronic injury after focal cerebral ischemia in mice.

METHODSFocal cerebral ischemia in mice was induced by middle cerebral artery occlusion (MCAO). Cilostazol was administrated intranasally or intraperitoneally 1 h, 4 h and 7 h after the operation; then twice a day from the second day for 2 weeks. The neurological deficit scoring and the inclined board testing were performed within 35 d after ischemia. The survival rate, infarct volume and neuron density were assessed 35 d after ischemia.

RESULTIntranasal cilostazol at 0.3 mg/kg increased the survival rate. Intranasal cilostazol (0.3 mg/kg, 1 mg/kg) and intraperitoneal cilostazol (10 mg/kg) significantly attenuated neurological deficit, reduced infarct volume, and increased the survival neuron density in the border of ischemia region.

CONCLUSIONCilostazol administered intranasally demonstrates protective effects on chronic cerebral ischemia in mice.

Administration, Intranasal ; Animals ; Brain ; drug effects ; pathology ; Brain Ischemia ; drug therapy ; pathology ; Disease Models, Animal ; Infarction, Middle Cerebral Artery ; drug therapy ; pathology ; Male ; Mice ; Neurons ; drug effects ; pathology ; Tetrazoles ; administration & dosage ; therapeutic use

OBJECTIVETo study the toxicological effects of benzo[a]pyrene(BaP) on mammalian animal's nerve tissue.

METHODS50 Kunming mice were divided into 5 groups at random, the exposed groups(3 dose level groups), the vehicle control group and standard control group. Every group got 10 mice. The exposed groups were treated by intraperitoneal injection with BaP dissolved in vegetable oil at 7.8, 3.2 and 1.3 mg/kg respectively, 4 times/week, for 10 weeks, the vehicle control group were given vegetable oil and the standard control group were not given any treatment. All the mice were anesthetized with 0.02 mol/L pentobarbital and infused with 1.33 mol/L paraformaldehyde dissolved in PBS through heart after 10 weeks. Then the brain, spinal cord and sciatic nerve were removed. Slices of these tissues were made and morphological changes were observed by optical microscope and electron-microscope. Cell appoptosis was examined by TUNEL(TdT-mediated x-dUTP nick end labeling) method.

RESULTSMorphological observations showed tissue injury in BaP exposed groups. There were focal necrosis areas found in the high-dose group. The cell apoptosis rates in 3.2 and 1.3 mg/kg groups were 90.02%-94.22% and 62.45%-77.54% respectively, significantly higher than those of vehicle control group and standard control group(4.60%-5.57%).

CONCLUSIONBaP is neurotoxic. It could damage the nerve tissue as well as induce DNA breaks and cell apoptosis.

Animals ; Apoptosis ; drug effects ; Benzo(a)pyrene ; toxicity ; Brain ; drug effects ; pathology ; Dose-Response Relationship, Drug ; In Situ Nick-End Labeling ; Mice ; Sciatic Nerve ; drug effects ; pathology ; Spinal Cord ; drug effects ; pathology

OBJECTIVETo investigate the effect of 1, 2-dichloroethane (1, 2-DCE) on blood brain barrier.

METHODSAcute toxic encephalopathy model was copied with the consecutive static inhalation of 1, 2-DCE. The water content of brain tissue was measured, and the blood brain barrier permeability was detected with lanthanum nitrate. The brain microvascular endothelial cells and neuroglial cells were cultured in vitro, which were administrated with 1, 2-DCE. The cell morphologic structures were observed under light microscope and electron microscope.

RESULTS(1) The extracellular edema was most found in the cerebral tissue and the leakage of lanthanum particles through the barrier were found with the lanthanum tracking method. (2) The water content in cerebral cortex in the moderate and high dose groups was significantly higher than that in the control group and became severer with the increases of the intoxicated time. The water content in cerebral medulla was significantly increased only at 6 hours after the intoxication. (3) The normal morphological structure of brain microvascular endothelial cells and neuroglial cells could be injured by 1, 2-DCE, and the injury to neuroglial cells caused by 1, 2-DCE occurred earlier and severer than that to brain microvascular endothelial cells.

CONCLUSION1, 2-DCE can damage blood brain barrier and induce cerebral edema.

Administration, Inhalation ; Animals ; Blood-Brain Barrier ; drug effects ; Brain ; pathology ; Brain Edema ; chemically induced ; pathology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Endothelial Cells ; drug effects ; pathology ; Ethylene Dichlorides ; toxicity ; Female ; Male ; Rats ; Rats, Sprague-Dawley

Animals ; Brain ; drug effects ; pathology ; Humans ; Hypothalamo-Hypophyseal System ; drug effects ; Neuroprotective Agents ; pharmacology ; Pituitary-Adrenal System ; drug effects ; Receptors, GABA-A ; drug effects ; Receptors, Glucocorticoid ; drug effects ; Receptors, N-Methyl-D-Aspartate ; drug effects ; Steroids ; pharmacology

AIMTo observe the effects of lidocaine and thiopental on the neuronal injury induced by the experimental ischemia in hippocampus slice cultures obtained from postnatal 22 days SD rats.

METHODSModel of the experimental ischemia was produced by hypoxia and glucose deprivation. Propidium iodide (PI) assay was used to observe the neuronal injury in CA1 and dentate gyrus (DG).

RESULTSAfter experimental ischemia, the peak of PI index was appeared in CA1 and DG on the first day (P < 0.01), PI index in DG was less than in CA1 (P < 0.01). PI indices were still higher during seven days after the experimental ischemia than before the experimental ischemia (P < 0.01). 10 nmol/L and 100 nmol/L concentration of lidocaine could significantly decrease PI indices in CA1 and DG (P < 0.01). 250 nmol/L and 600 nmol/L concentration of thiopental also decreased the PI indices in CA1 and DG (P < 0.01). The neuronal injury peaks were postponed to the third day after the experimental ischemia by lidocaine and thiopental.

CONCLUSIONIt suggested that lidocaine and thiopental could decrease the neuronal injury in CA1 and DG induced by the experimental ischemia, and postpone the neuronal injury peaks to the third day after the experimental ischemia.

Animals ; Brain Ischemia ; pathology ; CA1 Region, Hippocampal ; drug effects ; pathology ; In Vitro Techniques ; Lidocaine ; pharmacology ; Neurons ; drug effects ; pathology ; Rats ; Thiopental ; pharmacology