低分子肝素超氧化物歧化酶结合物对白细胞介素6转基因小鼠局灶性脑缺血模型星形胶质细胞的影响

BACKGROUND： Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect.
OBJECTIVE： To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 （IL-6） overexpressing mice following local cerebral ischemia.
DESIGN, TIME AND SETTING： Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005.
MATERIALS： Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups： sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University.
METHODS： Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment.
MAIN OUTCOME MEASURES： The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy （x200）.
RESULTS： In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker.
CONCLUSION： The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.     

Effects of natural-cerebrolysin-containing serum on neurotoxicity and synaptogenesis in amyloid-beta 1-40-induced Alzheimer’s disease in vitro models

BACKGROUND： Neuronal loss, synapse mutilation, and increasing malnourished axons are pathologically related to Alzheimer＇s disease. Microtubule-associated protein 2 （MAP2） is of importance for neuronal, axonal, and dendritic generation, extension, and stabilization, as well as for the regulation of synaptic plasticity.
OBJECTIVE： To investigate the antagonistic effects of natural-cerebrolysin-containing serum on beta amyloid protein 1-40 （Aβ1-40）-induced neurotoxicity from the standpoints of cell proliferation, synaptogenesis, and cytoskeleton formation （MAP2 expression）. DESIGN, TIME AND SETTING： A paralleled, controlled, neural cell, and molecular biology experiment was performed at the Institute of Integrated Chinese and Western Medicine, Shenzhen Hospital, Southern Medical University between February 2006 and April 2008.
MATERIALS： PC12 cells, derived from the rat central nervous system, were purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences, China. A β1-40 was provided by Sigma, USA. Natural-cerebrolysin was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. The natural-cerebrolysin was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yixingye （Ginkgo Leaf） in a proportion of 1：2：2. Following conventional water extraction technology, an extract （1：20） was prepared. Each gram of extract equaled 20 grams of crude drug. In a total of 12 adult male New Zealand rabbits, six underwent intragastric administration of natural-cerebrolysin extract for 1 month to prepare natural-cerebrolysin-containing serum, and the remaining six rabbits received intragastric administration of physiological saline to prepare normal blank serum.
METHODS： An AIzheimer＇s disease in vitro model was induced in PC12 cells using Aβ1-40. The cells were incubated with varying doses of natural-cerebrolysin-containing serum （2.5%, 5%, and 10%）. Normal blank serum-treated PC12 cells served as a blank control group.
MAIN OUTCOME MEASURES： Through the use of inverted phase contrast microscope, cell morphology and neurite growth were observed, neurite length was measured, and the percentage of neurite-positive cells was calculated. Cell proliferation rate was determined by MTT assay, and MAP 2 expression was detected by fluorescent immunocytochemistry.
RESULTS： Following Aβ1-40 treatments, some PC12 cells were apoptotic/dying, and only a few short neurites were observed. Following interventions with natural-cerebrolysin-containing serum, the PC12 cells proliferated, there was an increased number of neurites, and neurite length was enhanced. After middle- and high-dose natural-cerebrolysin treatments, the percentage of neurite-positive cells, as well as the average length of neurites, was significantly greater than the normal blank serum-treated PC12 cells （P 〈 0.05 or P 〈 0.01）. Compared with the blank control group, MAP2 expression in the Aβ1-40-treated PC12 cells was significantly inhibited, and the cell proliferation rate was significantly decreased （P 〈 0.01）. Following incubations with natural-cerebrolysin-containing serum, MAP2 expression and cell proliferation rate in the PC12 cells were significantly increased in a dose-dependent manner, compared with treatments with blank control serum （P 〈 0.05 or P 〈 0.01 ）.
CONCLUSION： Natural-cerebrolysin exhibited antagonistic effects on neurotoxicity in Aβ1-40 induced Alzheimer＇s disease in vitro models. These effects were likely related to cell proliferation and the upregulation of intracellular MAP2 expression.     

Protective effects of prostaglandin E1 perfusion against spinal cord ischemia-reperfusion injury in a rabbit model*☆

BACKGROUND： Prostaglandin E1 （PGE1） is known to be protective in ischemia-reperfusion of heart, lung,renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE： To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING： Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS： Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used： prostaglandin E1 injectable powder,as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS： We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 （100 ng/kg/min）. MAIN OUTCOME MEASURES： The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS： All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group （P 〈 0.05）. The scores of hind li     

Therapeutic effect of naloxone on radiation optic neurapathy★

BACKGROUND: Radiation therapy is widely used to treat tumor of brain; however, irradiation of radiation into eye tissues may easily cause ischemia and hypoxia in retina and optic nerve tissue so as to induce radiation optic neurapathy. Noloxone is a specific antagonist of opiate receptor, and it can change injured effect of β-endorphin. OBJECTIVE: To observe the axoplasmic transport of optic nerve at various phases after radiation injury so as to investigate the mechanism and regularity of optic nerve injury; meanwhile, to verify the therapeutic effects of naloxone on radiation optic neurapathy. DESIGN: Randomized controlled animal study. SETTINGS: Medical College of Qingdao University, Changzhi Medical College. MATERIALS: A total of 40 healthy adult New Zealand rabbits, weighing 2–2.5 kg, of either gender, were checked by using slit lamp and ophthalmoscop before radiation in order to exclude eye diseases. FCC-7000 vertical kilocurie 60Co therapeutic machine was made in Yantai, China; in addition, naloxone was provided by Beijing Sihuan Pharmaceutical Factory. METHODS: The experiment was carried out in the Animal Experimental Laboratory, Medical College of Qingdao University from January 2005 to December 2006. The experimental rabbits were randomly divided into radiation group (n =16), treatment group (n =16), blank control group (n =4) and injured control group (n =4). Except blank control group, rabbits in other three groups were irradiated in as the center of optic chiasma including the area of optic nerve by using 60Co therapeutic machine. Radioactive source was 85 cm away from head, and the size of operative field was 5 cm×5 cm. The radiation was performed once a day with the dosage of 3 Gy for 8 days in total. The total dosage was 24 Gy. When radioactive dosage reached 24 Gy, 2 mg/kg naloxone was dropped into ear vein of rabbits in the treatment group once a day for 10 days in total. Rabbits in the injured control group were only irradiated but not given any drugs. MAIN OUTCOME MEASURES: At 1, 10, 30 and 60 days after 24-Gy radiation, anterogradely labeled horseradish peroxidase (HRP) was used to measure optical density mean (OPTDM) in the radiation group and the treatment group; while, OPTDM was directly measured in the blank control group, and OPTDM was directly measured after radiation in the injured control group. RESULTS: All 40 experimental rabbits were involved in the final analysis. There were significant differences in OPTDM at various phases between radiation group and blank control group (P < 0.05); in addition, there was significant difference in OPTDM in the treatment group at 1, 10, 30 and 60 days after 24-Gy radiation (P < 0.05); otherwise, at 30 and 60 days after 24-Gy radiation, there was significant difference in OPTDM between radiation group and treatment group (P < 0.05). CONCLUSION: Naloxone may improve optic nerve axoplasmic transport disorder induced by radiation so as to protect optic nerve.     

Acupuncture at the “Huatuojiaji” point affects nerve root regional interleukin-1 level in a rat model of lumbar nerve root compression

BACKGROUND：It has been shown that interleukin-1 （IL-1） may cause inflammatory reactions, which stimulate the nerve root of patients with lumbar intervertebral disc protrusion and leads to pain. Whether the clinical curative effects of acupuncture in the treatment of lumbar and leg pain are linked to an inhibition of local IL-1 secretion is unknown. OBJECTIVE： To assess the influence of acupuncture on IL-1, this study was designed to verify the effects of acupuncture at the ＂Huatuojiaji （Extra）＂ point on the nerve root in a rat model of lumbar nerve root compression, compared with administration of meloxicam, a non-steroidal anti-inflammatory drug. DESIGN, TIME AND SETTING： Randomized, controlled, molecular biology experiment, performed at the Experimental Center, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University between September 2005 and April 2006. MATERIALS： Forty healthy adult Sprague Dawley rats of either gender were included in this study. The rats were randomly and evenly divided into the following four groups： normal control, model, acupuncture and meloxicam groups. Lumbar nerve root compression was induced in rats in the model, acupuncture, and meloxicam groups by inserting a specially made silicon rubber slice at the juncture of the L5 nerve root and the dural sac. The acupuncture needle （pattern number N3030, 30#, 1.5 inch） was purchased from Suzhou Medical Appliance Factory, China. IL-1 enzyme linked immunosorbent assay （ELISA） kit was purchased from Santa Cruz Biotechnology, Inc., USA. METHODS： The acupuncture group was acupunctured at the ＂Huatuojiaji＂ point, which is lateral to the compressed L5-6 nerve root, with an acupuncture depth of 0.5 cm. There were two treatment courses, each of involved seven 20-minute acupuncture sessions, one session a day. The meloxicam group was administered intragastrically 3.75 mg/kg meloxicam （5 mg meloxicam /10 mL physiological saline）. Rats in the normal control group and model group received an intragast     

Effects of different concentrations of celecoxib on proliferation and cell cycle of SH-SY-5Y cells and its mechanisms*★ In vitro study

BACKGROUND： Highly selective cyclooxygenase-2 （COX-2） inhibitors have recently been approved for the treatment of colon cancer, breast cancer, urinary bladder cancer, and skin cancer. For the highly selective COX-2 celecoxib, the mechanism of action for inhibiting neuroblastoma cells is still uncertain.
OBJECTIVE： To observe the influence of different celecoxib concentrations on proliferation and cell cycle of SH-SY-5Y cells in vitro and to reveal potential COX-2-independent mechanisms of celecoxib on SH-SY-5Y cells.
DESIGN： Controlled experiment.
SETTING： Department of Hematology, Affiliated Hospital of the Qingdao Medical College, Qingdao University, Shandong Province. MATERIALS： The study was performed at the Cerebrovascular Disease Institute of Shandong Province and the Laboratory of Molecular Biology, Affiliated Hospital of Qingdao Medical College, Qingdao University between September 2006 and June 2007. The SH-SY-5Y cell line was obtained from the Department of Molecular Biology, Qingdao Medical College, Qingdao University. Celecoxib was obtained from Pfizer Pharmaceuticals LLC, USA. Coulter DNA PREP reagent kit was purchased from Beckman Coulter, Inc. The antibodies against human CyclinD1, P21, and P16 were purchased from Santa Cruz Biotechnology. METHODS： SH-SY-5Y cells were treated with different concentrations of celecoxib （10, 20, 40, and 80 la mol/L） for 48 hours and comprised the experimental groups. The same concentrations of DMSO （dimethyl sulphoxide） treatment for 48 hours served as the control group.
MAIN OUTCOME MEASURES： ① Cellular morphology of cells pre-treated and post-treated with celecoxib by inverted microscopy. ② Methabenzthiazuron assay was used to measure cell proliferation. ③ Cell cycle was measured by flow cytometry after incubation with different celecoxib concentrations for 48 hours. ④CyclinD1, P16, and P21 protein expression was detected by Western blot analysis. RESULTS： ① Cellular morphology： The shape of SH-SY-5Y cells pre-treated     

Influence of Ganoderma lucidum spores on the levels of neuropeptide Y and somatostatin in brains of seizure rats*★

BACKGROUND： Previous research has revealed that somatostatin can induce epilepsy, and that the levels of neuropeptide Y may increase and become more active in brain areas with epileptic seizures. OBJECTIVE： To observe the effect of Ganoderma luciclum spore powder on the neuropeptide Y and somatostatin content in the cerebral cortex and hippocampal regions of seizure rats induced by pentylenetetrazol （PTZ）. Furthermore, to verify any effect of Ganoderma lucidum spore powder on inhibition of epileptic seizures. DESIGN, TIME AND SETTING： A randomized group animal study was performed in August 2007 in the School of Basic Medical Sciences, Jiamusi University （Jiamusi, Heilongjiang, China）. MATERIALS： Thirty healthy, male, Wistar rats, aged 12 weeks and weighing 180-220 g, were taken as the experimental animals. PTZ （Sigma Company, United States） was used to induce epilepsy. Ganoderma lucidum spores （Leyss, ex Fr variety） were purchased from Jiamusi City Wild Growing Case of the Ganoderma Lucidum （China）. Rabbit anti-somatostatin antibodies and secondary antibodies were purchased from Wuhan Boster Company （China）. Neuropeptide Y radioimmunoassay kit was purchased from Beijing Furui Biotechnology Company （China）. METHODS： Thirty rats were randomly divided into three groups： a control group, an epilepsy model group and a Ganoderma lucidum spore-treated group. Each group contained 10 animals. Rats in the epilepsy model group were treated with intraperitoneal injections of PTZ and gastric perfusion of physiologic saline. In the Ganoderma lucidum spore-treated group, intraperitoneal injection of PTZ and gastric perfusion of Ganoderma lucidum spore powder were administered. The blank control group was only administered with the physiological saline by intraperitoneal injection and gastric perfusion. MAIN OUTCOME MEASURES： Immunohistochemical staining and radioimmunoassay methods were used to observe the changes of somatostatin and neuropeptide Y content in brain tissue of epileptic r     

Morinda citrifolia L.(noni) and memantine attenuate periventricular tissue injury of the fourth ventricle in hydrocephalic rabbits

This study was designed to evaluate the neuroprotective effects of Morinda citrifolia L. (Rubiaceae), commonly known as noni, and memantine (a N-methy-D-aspartate receptor inhibitor) on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine (20 mg/kg, intraperitoneally; memantine-treated group) or noni (5 mL/kg, intragastrically; noni-treated group) was administered daily for 2 weeks. Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining density was significantly decreased in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3-positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle.     

Dynamic changes in fibrinogen levels of patients with acute cerebral infarction after taking defibrase*☆

BACKGROUND： At present, as a therapeutic drug mainly for reducing fibrinogen （FIB） levels, the dynamic influence of defibrase on the FIB levels of patients with acute cerebral infarction has not been clearly ascertained. OBJECTIVE： To observe the dynamic changes in FIB levels of patients with acute cerebral infarction at different time points after taking defibrase. DESIGN, TIME AND SETTING： Randomized controlled clinical trial. The study was conducted in the Department of Neurology, the Second Affiliated Hospital of Jinan University, from June to November 2006. PARTICIPANTS： Sixty patients with acute cerebral infarction, who had been treated by the Neurological Department of the Second Affiliated Hospital of Jinan University from June to November 2006, were selected, including 37 males and 23 females, aged 35-75 years. All cases met the diagnostic criteria formulated by the Fourth National Cerebrovascular Disease Conference within 12 hours of onset. All the patients were confirmed with definite hemiparesis and cerebral infarction without coma, and were randomly divided into two groups： a treatment group （n =40） and a control group （n =20）. Patients＇ families had the right to be informed and agree with the treatment, which had permission from the Hospital Ethics Committee. METHODS： Patients in the control group were given routine treatment with 30 mL fleabane and 0.75 g cytidine diphosphate added to 500 mL saline solution once a day for 14 consecutive days. Patients in the treatment group were given routine treatment and Haiwang defibrase injection （purchased from Changchu Guoao Bio-Pharmaceutical Co. Ltd., Approval document number H10983237） within 12 hours of infarction. Defibrase doses of 15, 12.5 and 10 U were given over 2 hours according to the patients＇ pre-treatment plasma FIB levels of ≥ 4.50 g/L, 3.50 4.49 g/L and 1.00 3.49 g/L, respectively. Plasma FIB levels in the treatment group were measured before, and once every six hours for 48 hours after administration of defib     

Correlation between changes of central neurotransmitter expression and stress response in mice*☆ A restraint time-course analysis

BACKGROUND： Changes in central neurotransmitter expression play an important role in stress response and forms the basis for stress-induced psychological and behavior changes.
OBJECTIVE： To observe the effects of different restraint stress intervals on brain monoamine neurotransmitter expression, and to investigate the correlation between stress response and neurotransmitter levels.
DESIGN： Randomized controlled animal study.
SETTING： Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University.
MATERIALS： Sixty 7-week-old male Kunming mice of clean grade, weighing 18-22 g, were provided by the Guangdong Medical Experimental Animal Center. The experiment was in accordance with animal ethics standards.
METHODS： This study was performed at the Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University from June 2006 to May 2007. A restraint device for mice was constructed according to published reports. Experimental mice were adaptively fed for 1 week and randomly divided into a control group （n = 10） and an experimental group （n = 50）. The experimental group was sub-divided into five restraint intervals： 4, 8, 12, 18, and 24 hours （n = 10 mice per time point）. Animals in the experimental group were not allowed to eat or drink during the restraint period. Mice in the control group did not undergo restraint, but had identical food and water restrictions. Cerebral cortex and hypothalamus were separated based on observational times and protein was extracted using perchloric acid. Central monoamine neurotransmitter levels were measured using high performance liquid chromatography with electrochemical detection. MAIN OUTCOME MEASURES： Levels of norepinephrine （NE）, dopamine hydrochloride （DA）, 3,4-dihydroxyphen-ylanetic acid （DOPAC）, homovanillic acid （HVA）, 5-hydroxytryptamine （5-HT）, and 5-hydroxyindoleac-etic acid （5-HIAA） in the cerebral cortex and hypothalamus of mice. RESULTS： Sixty mice were i     

Gastrodin protects neonatal rat brain against hypoxic-ischemic encephalopathy★ Acute therapeutic drug effects

BACKGROUND： Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however, the underlying mechanism has not been fully elucidated.
OBJECTIVE： The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain tissue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia. DESIGN： Single-factor design.
SETTING： Department of Pediatrics, Affiliated Hospital of Yanbian University.
MATERIALS： This study was performed in the Laboratory of the Department of Pediatrics, Affiliated Hospital of Yanbian University （key laboratory of provincial Health Department） from April to December 2003. Fifty-five Wistar rats of either gender, aged 7 days, were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University. The rats were randomly divided into normal control （n =10）, model （n = 15）, gastrodin-treated （n = 15）, and Danshen-treated （n = 15） groups. The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals. The following reagents were. used： Gastrodin （Sancai Medicine Group Co., Ltd., Zhongshan, Guangdong Province, China; component： gastrodin）, Danshen （Conba Stock Company, Jinhua, Zhengjiang Province, China; component： salvia miltiorrhiza）, and reagent kits for ^125I-prostaglandin B2 and ^125I-6-prostaglandin F l a （Research and Development Center for Science and Technology, General Hospital of Chinese PLA）.
METHODS： Rats in the normal control group received no treatment. Rats in the remaining 3 groups were anesthetized, followed by ligation of the left common carotid artery. One hour later, the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air （2.0 3.0 L/min） for 2 hours to develop hypoxic-ischemic encephalopathy. Immediately after lesion, rats     

Influence of leptin on luteinizing hormone and follicle stimulating hormone secreted from cultured rat anterior pituitary cells☆

BACKGROUND： Leptin may regulate reproductive function via release of hypothalamic neuropeptide Y. However, it is unknown whether this regulatory effect is limited to the hypothalamus. OBJECTIVE： To detect the effect of different dosages of leptin on luteinizing hormone （LH） and follicle stimulating hormone （FSH） secretion from in vitro cultured rat anterior pituitary cells. DESIGN： Contrast study based on cells. SETTING： This study was performed in the Basic Institute of Chengde Medical College, Chengde City, Hebei Province, China from March to June 2007. MATERIALS： Eighteen female Wistar rats of three months of age, weighing 200-220 g, and of clean grade were used. Leptin was provided by Peprotech Company, DMEM culture medium by Invitrogen Company, and the radioimmunological kit by Beijing Zhongshan Jinqiao Biotechnology Co., Ltd. METHODS： Three glandular organs were regarded as one group for culture of anterior pituitary cells. In the control group, saline was added to the culture medium instead of leptin. In the leptin group, leptin was prepared into different concentrations of 1×10^-12, 1×10^-11, 1×10^-9, 1×10^-7, and 1×10^-6 mol/L for stimulation of cultured cells. The culture supernatant was obtained at three hours after additional of saline/leptin. MAIN OUTCOME MEASURES： Contents of LH and FSH were detected by radioimmunology. RESULTS： Following leptin stimulation, LH release increased with increasing concentrations of leptin up to 1×10^-9 mol/L, where LH release peaked. LH release then progressively decreased with increasing leptin concentrations （P 〈 0.01）. LH release in the leptin （1×10^-12, 1×10^-11, 1×10^-7, and 1×10^-6 mol/L） groups was significantly higher than that in the control group （P 〈 0.01）. FSH content in the leptin （1×10^-11, 1×10^-9, and 1×10^-7 mol/L） groups was significantly higher than that in the control group （P 〈 0.01）. CONCLUSION： Leptin can directly affect pituitary tissue to promote the secretion of LH and FSH in a d     

Effects of acrous gramineus and its component, alpha-asarone, on apoptosis of hippocampal neurons after seizure in immature rats**☆

BACKGROUND： α-asarone and acrous gramineus have been shown to play a necessary function in enhancing the reactivity and convulsant threshold to electric stimulation of immature rats. They have also been shown to effectively suppress epileptic seizures induced by pentylenetetrazol in young rats. However, the mechanisms for these roles have been still unclear. OBJECTIVE： To observe the effects in immature rats of acrous gramineus and α -asarone on apoptosis of hippocampal neurons after epileptic seizure at the protein level, and to analyze the mechanism for these effects. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Pediatrics, First Hospital of Jilin University; Department of Histology and Embryology, Norman Bethune Medical School of Jilin University; Department of Internal Medicine, Children＇s Hospital of Changchun City; Department of Neurology, First Clinical Hospital affiliated to Harbin Medical University. MATERIALS： Fifty 3-week old Wistar rats, 34-40 g, irrespective of gender, were provided by Gaoxin Research Center of Medical Animal Experiment, Changchun. The animals were treated according to the animal ethical standards. The following chemicals were used for this study： acrous gramineus powders or infusion （Batch No, 0307113, Tianjiang Medicine Company Limited, Jiangyin）, α-asarone tablets （Batch No. 030219, Tianwei Pharmaceutical Factory, Shenyang）, and phenobarbital sodium tablets （Batch No. 020608, Xinya Medicine Company Limited, Shanghai）. The animals were divided into five groups randomly. First, ten rats were chosen as the normal controls. The remaining rats were treated with i.p. injections of pentylenetetrazol to stimulate an epileptic model. METHODS： The experiments were performed at the Neurological Laboratory of the First Hospital of Jilin University between October and December 2004. The rats were treated with i.p. injections of pentylenetetrazol （60 mg/kg） to establish an epileptic model. According to Racine＇ s standard, animal     

Influence of Ginkgo Biloba extract on beta-secretase in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions

BACKGROUND： Preparation of Ginkgo leaf has been widely used to improve cognitive deficits and dementia, in particular in Alzheirner＇s disease patients. However, the precise mechanism of action of Ginkgo leaf remains unclear. OBJECTIVE： To explore the effect of Ginkgo Biloba extract （Egb761）, Ginaton, on β -secretase expression in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions. DESIGN, TIME AND SETTNG： Completely by randomized, grouping study. The experiment was performed at the Laboratory of Molecular Imaging, Southeast University between August 2006 and August 2007. MATERIALS： A total of 128 Wistar rats aged 24 hours were selected, and hippocampal neurons were harvested for primary cultures. METHODS： On day 7, primary hippocampal neuronal cultures were treated with Egb761 （0, 25, 50, 100, 150, and 200μg/mL） under hypoxic/hypoglycemic or hypoglycemic culture conditions for 12, 24, and 36 hours, respectively. Hippocampal neurons cultured in primary culture medium served as control. MAIN OUTCOME MEASURES： Cell viability was assayed using 3-（4,5-Dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTT）; fluorescence detection of β -secretase activity was performed; Western Blot was used to measure β -secretase expression. RESULTS： Cell viability under hypoxic/hypoglycemic or hypoglycemic culture conditions was significantly less than control cells （P 〈 0.05）. Under hypoxic/hypoglycemic or hypoglycemic culture conditions, treatment with 25 μg/mL Egb761 did not alter cell viability. However, 〉 25 μg/mL Egb761 induced greater cell viability （P 〈 0.05）. No differences were observed between hypoxic/hypoglycemic or hypoglycemic cells （P 〉 0.05）. α -secretase activity was increased after 12 hours in hypoxic/hypoglycemic culture （P 〈 0.01）. There were no significant differences between the 12-, 24-, or 36-hour Egb761 groups and the hypoxic/hypoglycemic groups （P 〉 0.05）. β -secretase activity was greater after     

Naoxintong dose effects on inflammatory factor expression in the rat brain following focal cerebral ischemia

BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B （ kB）, interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia. DESIGN, TIME AND SETTING： The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIALS： A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320g, were selected. Naoxintong powder （mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis） was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608. METHODS： The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 g/kg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage All rats were administered by gavage at 5 and 23 hours following surgery, and subsequently, once per day. MAIN OUTCOME MEASURES： At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor- α, and complement 3 was examined by immunohistochemistry. RESULTS： A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as well as the high-dose, mo     

早年创伤对认知功能影响的研究进展

早年创伤是一个全球普遍存在的问题,严重影响儿童、青少年的大脑发育,继而导致认知功能、人格水平、社会行为的改变。早年创伤主要是父母、监护人或其他年长者对孩子施加躯体虐待、躯体忽视、情感虐待、情感忽视或性虐待。美国一项调查显示：儿童虐待事件的发生率高达1．2％[1]。早年创伤影响认知功能的多个领域,包括学习／工作记忆、视觉空间能力、执行功能、言语智能、复杂推理搜决策、学业表现等比]。创伤造成的认知功能改变是目前国内外神经科学和精神医学领域研究的热点,但其发病机制仍不明确,鉴于早年创伤与认知功能的关系问题,现就早年创伤对大脑发育、神经认知的影响加以综述。     

Activation of extrasynaptic GABA. receptors inhibits cyclothiazide- induced epileptiform activity in hippocampal CA1 neurons

Extrasynaptic GABAA receptors （GABAARs）-mediated tonic inhibition is reported to involve in the patho- genesis of epilepsy. In this study, we used cyclo- thiazide （CTZ）-induced in vitro brain slice seizure model to explore the effect of selective activation of extrasynaptic GABAARS by 4,5,6,7-tetra- hydroisoxazolo[5,4-c] pyridine-3-ol （THIP） on the CTZ-induced epileptiform activity in hippocampal neurons. Perfusion with CTZ dose-dependently induced multiple epileptiform peaks of evoked population spikes （PSs）in CA1 pyramidal neurons, and treatment with THIP （5 μmol/L） significantly reduced the multiple PS peaks induced by CTZ stimulation. Western blot showed that the 6-subunit of the GABAAR, an extrasynaptic specific GABAAR subunit, was also significantly down-regulated in the cell membrane 2 h after CTZ treatment. Our results suggest that the CTZ-induced epileptiform activity in hippocampal CA1 neurons is suppressed by the activation of extrasynaptic GABAARs, and further support the hypothesis that tonic inhibition mediated by extrasynaptic GABAARs plays a prominent role in seizure generation.     

Chaotic electrical stimulation of the subthalamic nucleus – mossy fiber sprouting, epileptic seizures, and brain electrical activity in pentylenetetrazol-kindled rats★

BACKGROUND： Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure. OBJECTIVE： This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention. DESIGN, TIME AND SETTING： This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007. MATERIALS： Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC-2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system （KT-88-2400） and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA. METHODS： The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups： （1） pre-stimulation （n = 10）, pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; （2） synchronous stimulation （n = 10）, rats received pentylenetetrazol and chaotic electrical stimulation concurrently; （3） post-administration stimulation （n = 10）, after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; （4） sham-stimulation （n = 10）, following pentylenetetrazol administration, an electrode was con     

Effect of Panax notoginseng saponins on the expression of beta-amyloid protein in the cortex of the parietal lobe and hippocampus, and spatial learning and memory in a mouse model of senile dementia

BACKGROUND： The pharmacological actions of Panax notoginseng saponins （PNS） lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer＇s disease. OBJECTIVE： Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein （App） and β -amyloid （A β ）, to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 （SAMP8） and compare the effects with huperzine A. DESIGN, TIME AND SETTING： A completely randomized grouping design, controlled animal experiment was performed in the Center for Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS： Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups： PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. （batch No.： Z53021485, Yuxi, Yunan Province, China）. Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. （batch No.： 20040801, Zhejiang, China）. METHODS： The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES： After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency （time-to-platform）, and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice w