ABSTRACT
Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.
ABSTRACT
OBJECTIVE: To study changes of glial fibrillary acidic protein (GFAP) expression and neural apoptosis in rat hippocampus and cortex of cesarean delivered offspring. METHODS: Thirty-eight pregnant SD rats were randomly allocated into 2 groups: 19 rats in vaginal delivery (VD) and 19 rats in cesarean section (CS). Forty-eight fetuses born by VD were kept intact, 40 fetuses were delivered by CS on day 21 of gestation. The fetal brain tissues were taken out on postnatal day 30 and 115, the expression profiles of GFAP in hippocampus and cortex were measured by immunohistochemical staining and western blot. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: (1) The expression profiles of GFAP: on postnatal day 115, the mean number of GFAP-immunoreactive astrocytes of hippocampus 29.7 ± 10.9 in VD group was significantly lower than 36.2 ± 2.8 in CS group (P < 0.05). The average GFAP-positive cells in the cortex of frontal lobe of 23.2 ± 4.6 in VD group was significantly lower than 36.8 ± 5.9 in CS group (P < 0.01). Likewise, on postnatal day 30, the mean number of GFAP-immunoreactive astrocytes of frontal cortex of 27.8 ± 6.0 in VD group was remarkably lower than 39.4 ± 4.5 in CS group (P < 0.01). The average GFAP-positive cells in the hippocampus of 31.5 ± 3.5 in VD group were not significantly lower than 37.2 ± 7.0 in CS group (P > 0.05). The expression of GFAP was detected in hippocampus and frontal cortex by western blot, however, there was no significant different expression of GFAP between VD group and CS group. (2) Neuronal apoptosis: TUNEL staining results indicated that, on postnatal day 115, fewer apoptotic cells scattered in offspring hippocampus subregion were only shown in CS group, never in VD group. No TUNEL positive staining cells were labeled in hippocampal subregion in VD group, therefore significantly lower than that of CS group (P < 0.05). CONCLUSIONS: There were different influences of cesarean section on GFAP expression in hippocampus or cortex in different developmental stage of offspring. Cesarean section might increase GFAP expression in the hippocampus and frontal cortex, even trigger neuronal apoptosis of hippocampus region.
Subject(s)
Apoptosis , Brain/metabolism , Cesarean Section/adverse effects , Glial Fibrillary Acidic Protein/metabolism , Animals , Astrocytes/metabolism , Blotting, Northern , Cerebral Cortex/metabolism , Delivery, Obstetric/methods , Female , Hippocampus/metabolism , Immunohistochemistry , Neurons , Pregnancy , Random Allocation , Rats , Rats, Sprague-Dawley , Up-RegulationABSTRACT
OBJECTIVE: This experiment evaluated the perinatal hypoxic effect on the retina of offspring of the ovoviviparous fish. ANIMAL STUDIED: The ovoviviparous fish Xiphophorous maculates was used for the experiment. PROCEDURE: The mothers were kept in a hypoxic environment of 3.5% oxygen for 6 h, starting 30 h before hatching. Subsequently, the retinae of the offspring were fixed, sectioned at 6 microm and evaluated microscopically from the age of 1 to 35 days. RESULTS: Degeneration of the outer nuclear layer of the retina was noted on the 3rd day and severe retinal degeneration was observed on the 35th day. Immunocytochemistry confirmed apoptosis by TUNEL reaction. There was no difference in neovascularization, as revealed by vascular endothelial growth factor, between controls (group 1) and hypoxic fish (group 2). CONCLUSIONS: Perinatal hypoxia could have long-lasting effects on the central nervous system in some species.
Subject(s)
Cyprinodontiformes , Fish Diseases/etiology , Hypoxia/veterinary , Retinal Degeneration/veterinary , Animals , Apoptosis , Fish Diseases/pathology , Hypoxia/complications , In Situ Nick-End Labeling/veterinary , Random Allocation , Retinal Degeneration/etiology , Retinal Degeneration/pathology , Retinal Neovascularization/veterinary , Species Specificity , Vascular Endothelial Growth Factors/metabolismABSTRACT
PURPOSE: To evaluate the feasibility of using a clinical 1.5T MR scanner to perform magnetic resonance (MR) diffusion tensor imaging (DTI) on in vivo rodent brains and to trace major rodent neuronal bundles with anatomical correlation. MATERIALS AND METHODS: Two normal adult Sprague Dawley (SD) rats were anesthetized and imaged in a 1.5T MR scanner with a microscopic coil. DTI was performed at a resolution of 0.94 mm x 0.94 mm x 0.5 mm (reconstructed to 0.47 mm x 0.47 mm x 0.5 mm, with b-factors of 600 seconds/mm2 and 1000 seconds/mm2) and a higher resolution of 0.63 mm x 0.63 mm x 0.5 mm (reconstructed to 0.235 mm x 0.235 mm x 0.5 mm, with a b-factor of 1500 seconds/mm2). The fiber-tracking results were correlated with corresponding anatomical sections stained to visualize neuronal fibers. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the neuronal fibers were measured and compared with results in published reports. RESULTS: Several major neuronal fiber tracts, including the corticospinal cord, corpus callosum, and anterior commissure, were identified in all DTI data sets. Stained anatomical sections obtained from the rats confirmed the location of these fibers. The ADC values (0.6-0.8 +/- 10(-3) mm2/second) of the fibers were similar to published figures. However, the FA values (0.3-0.35) were lower than those obtained in previous studies of white matter in rodent spinal cord. CONCLUSION: We have demonstrated the feasibility of using a 1.5T clinical MR scanner for neuronal fiber tracking in rodent brains. The technique will be useful in rodent neuroanatomy studies. Further investigation is encouraged to verify the FA values generated by DTI with such techniques.
Subject(s)
Brain/anatomy & histology , Diffusion Magnetic Resonance Imaging/methods , Animals , Anisotropy , Brain/physiology , Brain Mapping/methods , Feasibility Studies , Models, Animal , Rats , Rats, Sprague-DawleyABSTRACT
The aim of this study was to evaluate the outcome of treatment of pregnancy--induced hypertension (PIH) in rats by Ligustrazine collaborated with magnesium sulfate. PIH rat models were induced with Nomega-nitro-L-arginine methyl ester (L-NAME) infusing at 7 mg/kg per day via caudal vein for four days, then treated with Ligustrazine, magnesium sulfate, or both for three days. Rat blood pressure level was measured by the tail-cuff method, 24 hours urine protein was also assayed. The blood pressure and urine proteins of grouped PIH rats were recorded before the start and after the termination of therapy. The body length and the weight of fetal rats, the weight of placentals from pregnant rats were measured. The placental tissues, livers, kidneys of rats were investigated with integrated methods such as histopathologic observation with light microscopy, ultrastructural observation with transmission electron microscopy. L-NAME administration in pregnancy rats during the late pregnancy period had resulted in an rise of blood pressure, an increasing of urine protein, death rate of rat fetus, incidence of teratogenesis, and so on. Three groups of PIH rats treated with single magnesium sulfate, Ligustrazine, or Ligustrazine combined with magnesium sulfate showed an obvious dropping of the proteinuria, decompression of blood pressure (p<0.01, p<0.001), especially the treatment efficacy in the group of Ligustrazine combined with magnesium sulfate was more significant effective than other two groups (p<0.01, p<0.001). The treatment with both Ligustrazine and magnesium sulfate could increase the body length of newly born rats, the body weight of tomites and the placental weight, furthermore, reduce the rate of the teratosis of hindlimb-shortness (p<0.001). There were diffuse focal necrosis areas in the livers of PIH rats, their glomerular basement membrane had thickened extensively, the glomerular endothelium had swelled, extensive edema in the epithelia of renal tubule was demonstrated. The decidua and basal zone of the placentae of PIH rats all thickened, the microvilli of trophoblasts decreased. After treatment with ligustrazine especially with both Ligustrazine and magnesium sulfate, the necrosis of hepatocytes disappeared. The thickening of glomerular basement membrane in the group of ligustrazine or both Ligustrazine and magnesium sulfate treatment reduced; Moreover in the latter group the morphology of glomerular endothelium essentially recovered, the edema in cytoplasms of renal tubular epithelium reduced. The placental lesions were also relieved. The present results indicated the therapeutic effect by Ligustrazine collaborated with magnesium sulfate was better than a single use of Ligustrazine or magnesium sulfate. There were pathological alteration involved ischemia and anoxic in the placental tissues of PIH rats, resembled the placental pathological alteration of the human cases with PIH. The treatment with ligustrazine, and especially both Ligustrazine and magnesium sulfate in PIH rats could obviously relieve the lesions in lives, kidneys and placentae.
Subject(s)
Antihypertensive Agents/pharmacology , Magnesium Sulfate/pharmacology , Pyrazines/pharmacology , Animals , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Female , Hypertension, Pregnancy-Induced/drug therapy , Kidney/drug effects , Kidney/ultrastructure , Magnesium Sulfate/therapeutic use , Male , Microscopy, Electron, Transmission , Pregnancy , Pyrazines/therapeutic use , Rats , Rats, Sprague-DawleySubject(s)
Acute Lung Injury/pathology , Lung/pathology , Neovascularization, Pathologic , Animals , Disease Models, Animal , Female , Fibrosis , Lung/blood supply , Male , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To elucidate the possible relationship between pregnancy-induced hypertension syndrome (PIH) and expression of vimentin, type IV collagen and fibronectin in human placenta. METHODS: Nineteen pregnant women (PIH group) and 15 normal pregnant women (control group) matched for age and gestation were recruited. The expression of vimentin, type IV collagen and fibronectin in the placenta of PIH patients and normal subjects was investigated using immunohistochemical perioxidase-antiperoxidase (PAP) staining technique combined with an analysis through a computer-aided microphotographic system and compared between the two groups. RESULTS: The average grey value difference (GVD) which indicated positive staining of vimentin was 30 +/- 7 in section images of the moderate and severe PIH group, significantly lower than that of normal control group, 42 +/- 6 and mild PIH group, 42 +/- 9 (P < 0.01). The average GVD of type IV collagen in moderate and severe PIH group was 70 +/- 6, significantly higher than 29 +/- 4 of control group and 30 +/- 5 of mild PIH group (P < 0.001). The average GVD of fibronectin in moderate and severe PIH group was 37 +/- 4, significantly higher than that in control group, 31 +/- 4 and mild PIH group, 32 +/- 6 (P < 0. 05). CONCLUSIONS: There is tight relationship between abnormal expression of placental vimentin, type IV collagen, fibronectin and pathogenesis of PIH. Furthermore, the severity of PIH is positively correlated with the abnormal expression levels of those proteins.
Subject(s)
Collagen Type IV/metabolism , Fibronectins/metabolism , Hypertension, Pregnancy-Induced/metabolism , Placenta/metabolism , Vimentin/metabolism , Adult , Endothelium, Vascular/metabolism , Female , Humans , Hypertension, Pregnancy-Induced/etiology , Immunohistochemistry , PregnancyABSTRACT
OBJECTIVE: To observe the expression and distribution of substance P (SP), neurofilament-H (NFH) in glomus tumors with chronic pain, and to discuss the process of chronic pain and the relationship with pain degree. METHODS: Twenty-seven patients diagnosed as glomus tumor with chronic pain were enrolled as case group, and divided into light pain symptomatic group (LPSG) (n = 12) and severe pain symptomatic group (SPSG) (n = 15) according to clinical manifestations. Control group (CG) were enrolled by 30 patients with amputated extremities or hands after trauma. Immunohistochemical methods were used to determine the expression of SP, NFH which were detected quantitatively by computer graph analysis system too. RESULTS: The positive expression and distribution of SP, NFH existed in all the three groups and SPSG expression level was the highest [Grayscale Value(SP) (143.3 +/- 7.5), Grayscale Value(NFH) (167.7 +/- 4.4)], LPSG followed [Grayscale Value(SP) (156.2 +/- 8.2), Grayscale Value(NFH) (194.8 +/- 4.0)], control group was the third [Grayscale Value(SP) (208.2 +/- 16.6), Grayscale Value(NFH) (225.1 +/- 8.3)]; The difference of expression level among three groups was significant [SPSG vs LPSG (P(SP) = 0.002, P(NFH) < 0.0001), SPSG vs CG (P(SP) < 0.0001, P(NFH) < 0.0001), LPSG vs CG (P(SP) < 0.0001, P(NFH) < 0.0001)]. The findings of Pearson product-moment correlation analysis between quantitative grayscale value of SP, NFH respectively and pain score in all the patients with glomus tumor showed linear negative correlation (r(SP) = -0.8974, P(SP) = 0.000001; r(NFH) = -0.6545, P(NFH) = 0.000212). CONCLUSION: SP is the mainly afferent pain transmitter in the process of chronic pain in glomus tumor, and NFH plays an important role in pain-transmitted activities.