OBJECTIVETo observe the effects of electroacupuncture (EA) combined with Compound Salviae Miltiorrhizae Tablet (CSMT) on the expressions of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in hippocampus CA1 of chronic cerebral ischemia (CCI) rats.

METHODSTotally 50 Sprague-Dawley rats were randomly divided into the normal control group, the model group, the CSMT group, the EA group, and the EA +CSMT groups, 10 in each group. The CCI model was prepared by permanent bilateral common carotid arteries occlusion. One week after modeling, CSMT at 0.75 g/kg was given to rats in the EA + CSMT group and the CSMT group by gastrogavage, once daily, for 5 successive weeks. EA at Baihui (DU20) and Dazhui (DU14) was performed to rats in the EA group and the EA + CSMT group, lasting for 30 min, once daily, for 5 successive weeks. The expressions of BDNF and VEGF in the hippocampus CA1 area were detected by immunohistochemical assay and image analysis.

RESULTSCompared with the normal control group, the number of positively expressed BDNF and VEGF neurons and their expression intensity in the hippocampus CA1 of the model group obviously decreased (P < 0.01). Compared with the model group, the number of positively expressed BDNF and VEGF neurons and their expression intensity in the hippocampus CA1 of the CSMT group, the EA group, and the EA + CSMT groups obviously increased (P < 0.01, P < 0.05). The number of positively expressed BDNF and VEGF neurons and their expression intensity were obviously higher in the EA + CSMT group than those of the CSMT group and the EA group (P < 0.01).

CONCLUSIONSEA combined with CSMT could significantly increase the expressions of BDNF and VEGF in the hippocampus CA1 of CCl rats. Besides, their effects were significantly higher than those of the CSMT group or the EA group.

Animals ; Brain Ischemia ; metabolism ; therapy ; Brain-Derived Neurotrophic Factor ; metabolism ; CA1 Region, Hippocampal ; metabolism ; Electroacupuncture ; Male ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; Vascular Endothelial Growth Factor A ; metabolism

The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Abeta) but not with the extracellular APP/Abeta. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.
Advanced Glycosylation End Product-Specific Receptor ; Alzheimer Disease/genetics/*metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Astrocytes/*metabolism ; CA1 Region, Hippocampal/growth & development/metabolism/pathology ; Humans ; Mice ; Mice, Transgenic ; Neurons/*metabolism ; Receptors, Immunologic/genetics/*metabolism ; tau Proteins/genetics/metabolism

OBJECTIVETo evaluate the effect of physiological dose 17-β-estrodiol (E2) replacement therapy on vascular dementia caused by cerebral chronic hypoperfusion.

METHODSThe rats with bilateral common carotid artery occlusion (BCCAO) received E2 treatment starting from 3 days or 3 months after the operation. IgG leakage into the brain parenchyma and the changes of microvascular ultrastructure following BCCAO were examined using immunohistochemistry and electron microscopy, respectively; Western blotting was used to detect the expression of vascular endothelial growth factor (VEGF) protein.

RESULTSCompared with the sham-operated groups, the rats at 3 days and 3 months after BCCAO showed extensive vascular damages surrounded by IgG immunoreactivity in both the cortical and hippocampal CA1 regions. Stronger IgG immunoreactivity in the hippocampal CA1 region was observed at 3 days after BCCAO than at 3 months, but no significant IgG leakage was found in rats with continuous E2 treatment. Electron microscopy revealed severe edema around the blood vessels, mild vascular dilation, and endothelial cell damages at both 3 days and 3 months after BCCAO. E2 treatment markedly reduced the microvascular ultrastructural damages. Western blot analysis showed a significant increase in VEGF expression in the CA1 region at 6 h and 1 day after BCCAO followed by an obvious reduction till reaching the lowest level at 3 days; VEGF expression remained low even at 3 months after BCCAO and was significantly increased by E2 treatment.

CONCLUSIONSVascular structural damage occurs early after BCCAO and can last for 3 months. E2 replacement therapy at physiological doses can reduce the incidence of BCCAO-induced vascular dementia by up-regulating VEGF expression.

Animals ; Brain Ischemia ; pathology ; CA1 Region, Hippocampal ; metabolism ; pathology ; Dementia, Vascular ; drug therapy ; metabolism ; Disease Models, Animal ; Estradiol ; pharmacology ; Rats ; Transcriptional Activation ; Up-Regulation ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo investigate the neuroprotective effect of basic fibroblast growth factor (bFGF) on neurological function after hypoxic-ischemic brain damage (HIBD) in neonatal rats.

METHODSNinety-six HIBD models of neonatal Wistar rats were made by shearing right arteria carotis communis and then breathing 8% O(2)+92%N(2) for two hours. The models were divided into two groups randomly: the bFGF trial group and the normal saline control group. Each group had forty-eight rats. The other forty-eight neonatal Wistar rats were taken into the sham operation group. Forty rats were taken from each group and sacrificed on the 4 th, 7 th, 10 th, 17 th and 24 th days after the operation, respectively, The pathological changes in the brain were observed by optical microscope and the expressions of nestin and growth-associated protein-43 (GAP-43) in hippocampal CA1 region were examined with immunohistochemical staining and image quantitative analysis on the 4 th, 7 th, 10 th, 17 th and 24 th days after the operation. The spatial cognitive capability of other eight rats which were taken from each group respectively was evaluated by using the Morris water maze at the age of 30 days.

RESULTS(1) No brain damage was found in the sham operation group, the neurocytes were degenerative and necrotic in the control group of normal saline. The pathological manifestation of the brain damage in the bFGF trial group was milder than that of the normal saline control group. (2) Expression of nestin: The number of nestin-positive cells in hippocampal CA1 region of control group on the 4 th, 7 th, 10 th, 17 th and 24 th days after the operation was significantly increased compared with that of the sham operation group at all time points, and the numbers of nestin-positive cells in hippocampal CA1 region of the trial group were higher than those of the sham operation group and the control group (P < 0.01). (3) The expression of GAP-43 in hippocampal CA1 region of the neonatal rats reached peak on the 10th day after the operation in all the three groups. The integral optical density (IOD) of GAP-43 in hippocampal CA1 region of the control group was higher than that of the sham-operation group at all time points, and the IOD of GAP-43 in hippocampal CA1 region of the trial group was higher than those of the sham operation group and the control group at all time points (P < 0.01 for all). (4) The latency to escape platform in control group (51.75 +/- 11.27s) was longer than that in trial group (40.32 +/- 11.48s) and the sham operation group (36.58 +/- 10.83s) (P < 0.05); the frequency of passing through the platform in control group (2.34 +/- 2.42) was less than that in trial group (5.08 +/- 3.86) and the sham operation group (7.03 +/- 3.62) (P < 0.05). There was no significant difference between the trial group and the sham operation group (P > 0.05).

CONCLUSIONS(1) The expression of nestin and GAP-43 increased in hippocampal CA1 region of neonatal rats with HIBD, it may be involved in the activation of neural stem cells and the regeneration of neurocytes after HIBD. (2) The treatment with bFGF can improve the ability of learning and memory of neonatal rats with HIBD. (3) Exogenous bFGF could enhance the expression of nestin and GAP-43 in the brain of neonatal rats with HIBD, which may play an important role in restoration of neurons damaged due to hypoxia-ischemia.

Animals ; Animals, Newborn ; Brain ; drug effects ; pathology ; CA1 Region, Hippocampal ; pathology ; Fibroblast Growth Factor 2 ; therapeutic use ; GAP-43 Protein ; therapeutic use ; Hippocampus ; drug effects ; Hypoxia, Brain ; prevention & control ; Hypoxia-Ischemia, Brain ; prevention & control ; Intermediate Filament Proteins ; metabolism ; Ischemia ; prevention & control ; Maze Learning ; drug effects ; Nerve Tissue Proteins ; metabolism ; Nestin ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

OBJECTIVEIn recent years, some experiments on vitamin A-deprived animals reveal a progressive and ultimately profound impairment of hippocampal CA1 area's long-term potentiation and these losses are fully reversible by dietary vitamin A replenishment in vivo. Our previous study revealed that marginal vitamin A deficiency (MVAD) beginning from embryonic period impairs learning, memory and long-term potentiation (LTP) in young rats. But the losses might not be reversible if the vitamin A supplementation is late, especially when the critical period of hippocampus development is missed. The present study aimed to observe the recovery of learning and memory in vitamin A marginally deficient young rats after early intervention with vitamin A supplementation and begin to study the mechanism.

METHODSRats were divided into control, MVAD, vitamin A intervention 1 (VAI1) and VAI2 groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 U/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 U/kg). In VAI1 group (10 young rats) the dams were fed with MVAD diet till day 14 of pregnancy, then were fed with normal diet and the pups were fed with normal diet. In VAI2 group (13 young rats) the dams were fed with MVAD diet till delivery, then were fed with normal diet and the pups were fed with normal diet too. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique. The expression of RAR-alpha, RAR-beta, RXR-beta, RXR-gamma, RC3 and tTG mRNA was detected by using semi-quantified RT-PCR in hippocampus.

RESULTS(1) The times to reach the learning standard in MVAD group (45.6 +/- 12.1) were more than those in control group (17.1 +/- 4.4) (P < 0.01), in both VAI1 group (20.8 +/- 3.1) and VAI2 group (22.1 +/- 4.0) were more than those in group MVAD (P < 0.01), and there were no significant differences among groups VAI1, VAI2 and control (P > 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group [(22.9 +/- 9.4)%] and VAI2 group [(39.1 +/- 4.33)%] were less than that of control group [(57.5 +/- 27.3)%], respectively (P < 0.05). No significant difference was found between VAI1 and control group (P > 0.05). (3) The expression of RAR-beta and RXR-beta mRNA decreased by 48.72% and 37.84% respectively (P < 0.05) compared with control, but the expression of RAR-beta mRNA in group VAI1 was higher than that in group MVAD (P = 0.065). The expression of RC3 mRNA in MVAD group was lower than that in control (P = 0.061) and RAR-alpha mRNA in MVAD group was higher than that in control (P = 0.061). The expression of RXR-gamma and tTG mRNA had no significant difference among different groups as determined with semi-quantified RT-PCR in hippocampus.

CONCLUSIONEarly vitamin A intervention may make the impaired learning and memory behavior due to marginal vitamin A deficiency recover to the normal level in young rats, but lip losses in group VAI2 might not be reversible. Vitamin A may modulate the expression of RC3 mRNA by affecting RAR-alpha, RAR-beta and RXR-beta to influence the LTP, learning and memory.

Animal Nutritional Physiological Phenomena ; Animals ; CA1 Region, Hippocampal ; metabolism ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Memory ; drug effects ; Neurogranin ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Rats ; growth & development ; Receptors, Retinoic Acid ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transglutaminases ; genetics ; metabolism ; Vitamin A ; therapeutic use ; Vitamin A Deficiency ; drug therapy

To examine the effects of Populus tomentiglandulosa (PT) extract on the expressions of antioxidant enzymes and neurotrophic factors in the cornu ammonis 1 (CA1) region of the hippocampus at 5 min after inducing transient global cerebral ischemia (TGCI) in gerbils, TGCI was induced by occlusion of common carotid arteries for 5 min. Before ischemic surgery, 200 mg·kg PT extract was orally administrated once daily for 7 d. We performed neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B staining. Furthermore, we determined in situ production of superoxide anion radical, expression levels of SOD1 and SOD2 as antioxidant enzymes and brain-derived neurotrophic factor (BDNF) and insulin-like growth factor I (IGF-I) as neurotrophic factors. Pretreatment with 200 mg·kg PT extract prevented neuronal death (loss). Furthermore, pretreatment with 200 mg·kg PT extract significantly inhibited the production of superoxide anion radical, increased expressions of SODs and maintained expressions of BDNF and IGF-I. Such increased expressions of SODs were maintained in the neurons after IRI. In summary, pretreated PT extract can significantly increase levels of SODs and protect the neurons against TGCI, suggesting that PT can be a useful natural agent to protect against TGCI.
Animals ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Gerbillinae ; Humans ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; administration & dosage ; Populus ; chemistry ; Pyramidal Cells ; drug effects ; metabolism ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Superoxide Dismutase ; genetics ; metabolism ; Up-Regulation ; drug effects