Acute pathological changes of facial nucleus and expressions of postsynaptic density protein-95 following facial nerve injury of varying severity★ A semi-quantitative analysis

BACKGROUND： Previous studies have demonstrated that postsynaptic density protein-95 （PSD-95） is widely distributed in the central nervous system and is related to the development of the CNS and sensory signal transmission as well as acute or chronic nerve cell death following ischemic brain injury. OBJECTIVE： To semi-quantitatively determine the pathological changes of apoptotic facial neurons and the expression of PSD-95 in the facial nucleus following facial nerve injury of varying extents using immunohistochemical staining methods. DESIGN, TIME AND SETTING： Randomized, controlled animal experiments were performed in the Ultrasonic Institute of the Second Affiliated Hospital of Chongqing University of Medical Sciences from September to December 2007. MATERIALS： Sixty-five healthy, adult, Sprague-Dawley （SD） rats, both male and female, were used for this study. Rabbit anti-rat PSD-95 polyclonal antibody was purchased from Beijing Biosynthesis Biotechnology Co., Ltd. METHODS： SD rats were randomly assigned into a control group with five rats and three injured groups with 20 rats per group. Exposure, clamp and cut for bilateral facial nerve trunks were performed in the rats of the injury groups, and no injury was inflicted on the rats of the control group. MAIN OUTCOME MEASURES; The brainstems of all the rats were excised on days 1, 3, 7, and 14 post injury, and then the facial nuclei were stained with hematoxylin-eosin to observe any pathological changes due to apoptosis in facial neurons. PSD-95 expression in facial nuclei was detected by immunohistochemistry and the number of PSD-95 positive cells was counted under a light microscope. RESULTS： The expression of PSD-95 in the facial nucleus and morphology of the facial neuron within the exposure group had no obvious changes at various points in time tested （P 〉 0.05）. However, the expressions of PSD-95 in the facial nucleus of the clamp group and cut group increased on day 1 post injury （P 〈 0.05）, and showed further increase on d     

大鼠面神经切断和切断修复后面神经核内鞘脂激活蛋白原的变化

BACKGROUND： Studies have demonstrated that damaged facial nerves synthesize prosaposin to promote repair of facial neurons. OBJECTIVE： To observe time-course changes of prosaposin expression in the facial nerve nucleus of Sprague Dawley rats following facial nerve transection and repair. DESIGN, TIME AND SETTING： A randomized control neuropathological animal experiment was performed in Chongqing Medical University between March 2007 and September 2008. MATERIALS： A total of 48 adult, male, Sprague Dawley rats were selected and randomly divided into transection and transection ＋ end-to-end anastomosis groups （n =24）. Rabbit anti-rat prosaposin antibody, instant SABC immunohistochemical kit, and antibody dilution solution were purchased from Wuhan Uscn Science Co., Ltd., China. METHODS： In the transection group, the nerve trunk of the distal retroauricular branch of the left facial nerves was ligated in Sprague Dawley rats, and a 5-mm nerve trunk at the distal end of the ligation site was removed. In the transection ＋ end-to-end anastomosis group, epineurial anastomosis was performed immediately following transection of the left facial nerves. The right facial nerves in the two groups served as the normal control group. MAIN OUTCOME MEASURES： The number of prosaposin-positive neurons, as welt as intensity of immunostaining in facial nerve nucleus, following transection and end-to-end anastomosis were determined by immunohistochemistry at 1, 3, 7, 14, 21, and 35 days after injury. RESULTS： Transection group： transection of facial nerves resulted in increased number of prosaposin-positive neurons and immunoreactivity intensity in the facial nucleus on day 1. These values significantly increased by day 3. Expression was greater than in the control side. The peak of the reduction was reached at 7 days post-surgery. Transection ＋ end-to-end anastomosis group： the number of prosaposin-positive neurons and immunoreactivity intensity was reduced in the facial nerve nucleus following immediate end-to-end anastomosis on day 7 post-surgery. These values began to gradually increase by day 14 post-anastomosis. By day 35 post-anastomosis, the number of prosaposin-positive neurons in the operated side recovered to normal levels. The number of prosaposin-positive neurons, as well as immunoreactivity intensity, was significantly greater in the facial nerve nucleus, compared with the transection group on days 14, 21, and 35 post-surgery （P 〈 0.05）. The rhythmic whisking of vibrissa recovered, and recovery time was consistent with increased numbers of prosaposin-positive neurons. CONCLUSION： Within 7 days after injury, prosaposin expression in the facial nerve nucleus exhibited an initial increase, followed by a decrease, and was not affected by facial nerve repair. Following facial nerve damage, neural anastomosis was shown to increase prosaposin expression in the facial nerve nucleus after 14 days. Recovery of prosaposin occurred simultaneously with reinnervation.     

Low-intensity ultrasound for regeneration of injured peripheral nerve

BACKGROUND: Ultrasound is a kind of mechanical wave and characterized by mechanical effect, heat effect and physical and chemical effect. Ultrasound can promote regeneration of peripheral nerves after a slight injury based on its mechanical effect. However, whether it can promote regeneration of peripheral nerves after a severe injury or not is still unclear. OBJECTIVE: To study the effect of low-intensity ultrasound (LIU) on regeneration of injured peripheral nerve, through examining sciatic nerve function index, the sensory nerve conduction velocity and the thickness of myelin sheath. DESIGN: Single factor design of contrast observation. SETTING: Institute of Ultrasound Engineering, Chongqing Medical University. MATERIALS: A total of 64 female Wistar rats, of clean grade, aged 3 months, weighing 200－250 g, were provided by Experimental Animal Center of Chongqing Medical University. All rats were randomly divided into treatment group and control group with 32 in each group. In addition, rats were observed at 4 time points, including 2, 4, 6 and 8 weeks, with 8 at each time point. The main equipments were detailed as follows: forceps (Medical Treatment Apparatus Company, Chongqing), low-intensity ultrasound treatment instrument (Institute of Ultrasound Engineering in Medicine), the analysis instrument of diagram resembles and arithmetic figure (the United States Bio-RAD Company), ultrasound coupling agent (Xunde Image material factory, Hangzhou), Osmium Tetraoxide (Next Chimica, South Africa). METHODS: The experiment was carried out in Institute of Ultrasound Engineering of Chongqing Medical University from December 2003 to May 2004. The right sciatic nerves of 64 rats were crushed with forceps for 30 s to form the experimental animal models. Then they were treated at 3 days after operation. Rats in the treatment group received the LIU exposure. LIU was applied every other day to the crush site of rats, which had a spatial peak, time-averaged intensity of 0.25 W/cm2 operated at 1 MHz for 1 minute per application for total 8 weeks. At various stages after operation, the sciatic nerve function index(SFI), the sensory nerve conduction velocity and its histology were detected. Rats in the control received a sham exposure. MAIN OUTCOME MEASURES: SFI; sensory nerve conduction velocity; density of myelinated nerve fiber; velocity of nerve regeneration; histological examination. RESULTS: Among 64 Wistar rats, 2 were lost during the experiment and another 2 were supplied. ① Histological examination: Two weeks after treatment, degeneration of axis-cylinder and myelin sheath was obvious in treatment group as compared with that in control group. Within 4－8 weeks after treatment, regeneration of axis-cylinder and myelin sheath of nerve fiber was superior in treatment group to that in control group. At 8 weeks after treatment, axis-cylinder and myelin sheath in treatment group were closed to normal value. Quantity of nerve fiber was less in control group than that in treatment group and the arrangement was disorder. At 2, 4 and 6 weeks after treatment, proliferation of Schwann cells was superior in treatment group to that in control group. At 6 and 8 weeks after treatment, proliferation of fiber tissue in nerve was severer in control group than that in treatment group. ② SFI: At 4, 6 and 8 weeks after treatment, SFI was higher in treatment group than that in control group (t =8.00, 12.41, 15.13, P < 0.01). ③ Sensory nerve conduction velocity: At 2, 4, 6 and 8 weeks after treatment, sensory nerve conduction velocity was faster in treatment group than that in control group (t =11.74, 10.81, 3.51, P < 0.01). ④ Density of myelinated nerve fiber: At 2, 4, 6 and 8 weeks after treatment, density of myelinated nerve fiber was higher in treatment group than that in control group (t =2.16, P < 0.05; t =3.29, 3.52, 3.23, P < 0.01). ⑤ Velocity of nerve regeneration: Velocity of nerve regeneration was (1.50±0.08) mm/d and (1.22±0.10) mm/d of treatment group and control group, respectively. This suggested that velocity of nerve regeneration was faster in treatment group than that in control group (t =2.708, P < 0.05). CONCLUSION: LIU can promote the regeneration of injured peripheral nerve from the appearance, construction, function aspect and functional recovery. Its mechanism may be through the modulation and effect of many links of nerve regeneration process.     

促红细胞生成素与大鼠面神经损伤后运动神经元TNF-a及Bax的表达

This study sought to evaluate the effect of high-dose erythropoietin (EPO; 5 000 IU/kg) on the expression of tumor necrosis factor-alpha (TNF-α) and Bax in the facial nucleus after facial nerve transection in rats. A total of 42 Wistar rats of both genders were used in this study, and 40 rats were randomly divided into 2 groups: EPO group and model group. The EPO group was treated with EPO once a day for 5 days at a dose of 5 000 IU/kg body weight. The model group was treated with saline of the same amount. At day 3 after EPO (or saline) treatment, the right facial nerves of the 40 rats were transected at the level of the stylomastoid foramen, with the left sides untreated. The remaining 2 rats that did not undergo axotomy served as the control group. The surviving motor neurons in operated rats were counted in coronal paraffin sections of the facial nucleus. The expression of TNF-α and Bax in the facial nucleus was detected by immunohistochemical staining at days 3, 7, 14, 21, and 28 after axotomy. At days 14, 21, and 28 after facial nerve axotomy, a significantly greater proportion of facial motor neurons survived in the EPO group than in the model group. After axotomy, the expression of TNF-α and Bax increased in motor neurons in both the EPO and the model groups. TNF-α expression reached its peak level at day 14 after axotomy, while Bax expression reached its peak level at day 21. TNF-α expression was much lower in the EPO group than in the model group at all time points. No significant difference in Bax expression was found between the EPO and the model groups. These results indicate that high-dose EPO treatment attenuates the increase in TNF-α expression in the facial nucleus and reduces the loss of motor neurons after facial nerve transection in rats. However, high-dose EPO treatment has little effect on Bax expression.     

人参皂甙Rg1对去卵巢大鼠面神经核脑源性神经营养因子表达的影响：半定量分析

BACKGROUND： Estrogen is neuroprotective effects such as breast carcinoma, endometria but long-term estrogen treatment can induce side cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects. OBJECTIVE： To study the effects of Ginsenoside Rgl on facial neurons and brain-derived neurotrophic factor （BDNF） expression in the facial nucleus in ovariectomized rats. DESIGN, TIME AND SETTING： The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008. MATERIALS： Ginsenoside Rgl （Sigma, USA）, rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG （Boster, China）, and a TUNEL kit （Roche, Germany） were used in this study. METHODS： A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation （n = 8）, model （n = 20）, and Ginsenoside Rgl （n = 20） groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rgl group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rgl; other groups received 2 mL saline, once a day, for 14 days. MAIN OUTCOME MEASURES： Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry. RESULTS： At 3-14 days following facial nerve damage, Ginsenoside Rgl increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths （P 〈 0.05）. Ginsenoside Rgl also gradually increased Bcl-2 protein expression and decreased Bax protein expression （P 〈 0.05）. By day 7, apoptosis was observed in facial neurons, but Ginsenoside Rgl reduced the number of apoptotic neurons. Sham animals did not show any changes in BDNF, Bcl-2, or Bax expression or facial neuron morphology. CONCLUSION： Ginsenoside Rgl can substantially inhibit facial neuronal apoptosis by increasing endogenous BDNF and Bcl-2 expression and by decreasing Bax expression in ovariectomized rats after facial nerve damage.     

Combination therapy using evening primrose oil and electrical stimulation to improve nerve function following a crush injury of sciatic nerve in male rats

Peripheral nerve injuries with a poor prognosis are common. Evening primrose oil (EPO) has beneficial biological effects and immunomodulatory properties. Since electrical activity plays a major role in neural regeneration, the present study investigated the effects of electrical stimulation (ES), combined with evening primrose oil (EPO), on sciatic nerve function after a crush injury in rats. In anesthetized rats, the sciatic nerve was crushed using small haemostatic forceps followed by ES and/or EPO treatment for 4 weeks. Functional recovery of the sciatic nerve was assessed using the sciatic functional index. Histopathological changes of gas-trocnemius muscle atrophy were investigated by light microscopy. Electrophysiological changes were assessed by the nerve conduction velocity of sciatic nerves. Immunohistochemistry was used to determine the remy-elination of the sciatic nerve following the interventions. EPO + ES, EPO, and ES obviously improved sciatic nerve function assessed by the sciatic functional index and nerve conduction velocity of the sciatic nerve at 28 days after operation. Expression of the peripheral nerve remyelination marker, protein zero (P0), was in-creased in the treatment groups at 28 days after operation. Muscle atrophy severity was decreased significantly while the nerve conduction velocity was increased significantly in rats with sciatic nerve injury in the injury+ EPO + ES group than in the EPO or ES group. Totally speaking, the combined use of EPO and ES may pro-duce an improving effect on the function of sciatic nerves injured by a crush. The increased expression of P0 may have contributed to improving the functional effects of combination therapy with EPO and ES as well as the electrophysiological and histopathological features of the injured peripheral nerve.     

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.     

Facial nucleus up-regulation of brain-derived neurotrophic factor mRNA following electroacupuncture treatment in a rabbit model of facial nerve injury*★

BACKGROUND： The effect of acupuncture treatment on peripheral facial nerve injury is generally accepted. However, the mechanisms of action remain poorly understood. OBJECTIVE： To validate the effect of acupoint electro-stimulation on brain-derived neurotrophic factor （BDNF） mRNA expression in the facial nucleus of rabbits with facial nerve injury, with the hypothesis that acupuncture treatment efficacy is related to BDNE DESIGN, TIME AND SETTING： Peripheral facial nerve injury, in situ hybridization, and randomized, controlled, animal trial. The experiment was performed at the Laboratory of Anatomy, Heilongjiang University of Chinese Medicine from March to September 2005. MATERIALS： A total of 120 healthy, adult, Japanese rabbits, with an equal number of males and females were selected. Models of peripheral facial nerve injury were established using the facial nerve pressing method. METHODS： The rabbits were randomly divided into five groups （n = 24）： sham operation, an incision to the left facial skin, followed by suture; model, no treatment following facial nerve model establishment; western medicine, 10 mg vitamin B1, 50 ug vitamin B12, and dexamethasone （2 mg/d, reduced to half every 7 days） intramuscular injection starting with the first day following lesion, once per day; traditional acupuncture, acupuncture at Ytfeng, Quanliao, Dicang, Jiache, Sibai, and Yangbai acupoints using a acupuncture needle with needle twirling every 10 minutes, followed by needle retention for 30 minutes, for successive 5 days; electroacupuncture, similar to the traditional acupuncture group, the Yifeng （negative electrode）, Jiache （positive electrode）, Dicang （negative electrode）, and Sibai （positive electrode） points were connected to an universal pulse electro-therapeutic apparatus for 30 minutes per day, with disperse-dense waves for successive 5 days, and resting for 2 days. MAIN OUTCOME MEASURES： Left hemisphere brain stem tissues were harvested on post-operative days 7, 14, 21, and     

Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats★

BACKGROUND： Recently, grape seed procyanidin （GSP） has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis. OBJECTIVE： To study the effects of GSP on nerve growth factor （NGF） expression and neurological function following cerebral ischemia/reperfusion injury in rats. DESIGN： Randomized controlled study based on SD rats. SETTING： Weifang Municipal People＇s Hospital. MATERIALS： Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company （batch number： 20060107）. Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS： The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP （40 mg/kg） group, or low-dose GSP （10 mg/kg） group （n = 12 per group）. Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection （2 mL/kg i.p.） once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP （20 or 5 mg/mL i.p., respectively, 2 mL/kg） with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES： NGF expression in the     

Changes in brain-derived neurotrophic factor expression after transplanting microencapsulated sciatic nerve cells of rabbits into injured spinal cord of rats

BACKGROUND: Changes of brain-derived neurotrophic factor (BDNF) expression reflect function of nerve cells; meanwhile, they play a significant role in researching interventions on plerosis of nerve injury. OBJECTIVE: To observe and compare the effects on changes of BDNF expression in rats with spinal cord injury between microencapsulated sciatic nerve cells of rabbits and only transplanting sciatic nerve cells of rabbits. DESIGN: Randomized controlled animal study. SETTING: Medical School of Jiujiang College. MATERIALS: The experiment was carried out in the Medical Science Researching Center, Jiujiang College from May 2004 to May 2006. A total of 90 healthy adult SD rats, weighing 250–300 g, of either gender; and 10 rabbits, weighing 2.0–2.5 kg, of either gender, were provided by Jiangxi Experimental Animal Center. METHODS: Sciatic nerve tissue of rabbits was separated to make cell suspension. After centrifugation, suspension was mixed with 15 g/L alginate saline solution and ejaculated to 20 mmol/L barium chloride saline solution by double-cavity ejaculator. The obtained cell microcapsules were suspended in saline. Rats were randomly divided into microencapsulated group, only suspension group, and only injured group with 30 animals in each group. After anesthesia, T10 spinous process and vertebra lamina of rats in the former two groups were exposed. Spinal cord tissue in 2-mm length was removed from rats by spinal cord right hemi-section. The gelatin sponges with the size of 2 mm × 2 mm × 2 mm were grafted as filing cage, and absorbed 10 μL microencapsulated sciatic nerve cells of rabbit in the microencapsulated group and 10 μL sciatic nerve cells of rabbits in the only suspension group; respectively. No graft was placed in the only injured group. MAIN OUTCOME MEASURES: On the 1st, 3rd, 7th, 14th and 28th days after operation, immunohistochemistry (SABC technique) was used to detect distribution and amount of positive-reactive neurons in BDNF of spinal cord samples which were selected as 2 cm away from the injured surface. RESULTS: All the 90 rats were involved in the final analysis. Masses of brown-yellow particles were found in the microencapsulated group, and most of them were distributed in the spinal cord anterior horn neurons and glial cells. The positive-reactive neuron particles were also found in the white matter and gray matter. On the 3rd, 7th, 14th and 28th days after operation, amount of positive-reactive neurons in BDNF in the microencapsulated group was higher than that in the only injured group (P < 0.01) and only suspension group (P < 0.05). CONCLUSION: After transplanting microencapsulated nerve cell suspension into injured spinal cord of rats, distribution and amount of positive-reactive neurons in BDNF of local samples at injured surface are increased remarkably as compared with those by using tissue cell transplantation.     

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。     

Differential cognitive responses to guqin music and piano music in Chinese subjects： an event-related potential study

Objective To compare the cognitive effects of guqin （the oldest Chinese instrument） music and piano music. Methods Behavioral and event-related potential （ERP） data in a standard two-stimulus auditory oddball task were recorded and analyzed. Results This study replicated the previous results of culture-familiar music effect on Chinese subjects： the greater P300 amplitude in frontal areas in a culture-familiar music environment. At the same time, the difference between guqin music and piano music was observed in NI and later positive complex （LPC： including P300 and P500）： a relatively higher participation of right anterior-temporal areas in Chinese subjects. Conclusion The results suggest that the special features of ERP responses to guqin music are the outcome of Chinese tonal language environments given the similarity between Guqin＇s tones and Mandarin lexical tones.     

Brain network markers of abnormal cerebral glucose metabolism and blood flow in Parkinson＇s disease

Neuroimaging of cerebral glucose metabolism and blood flow is ideally suited to assay widely-distributed brain circuits as a result of local molecular events and behavioral modulation in the central nervous system. With the progress in novel analytical methodology, this endeavor has succeeded in unraveling the mechanisms underlying a wide spectrum of neurodegenerative diseases. In particular, statistical brain mapping studies have made significant strides in describing the pathophysiology of Parkinson＇s disease （PD） and related disorders by providing signature biomarkers to determine the systemic abnormalities in brain function and evaluate disease progression, therapeutic responses, and clinical correlates in patients. In this article, we review the relevant clinical applications in patients in relation to healthy volunteers with a focus on the generation of unique spatial covariance patterns associated with the motor and cognitive symptoms underlying PD. These characteristic biomarkers can be potentially used not only to improve patient recruitment but also to predict outcomes in clinical trials.     

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     

Effect of Ganoderma lucidum spore on expression of insulin-like growth factor-1, nuclear factor-kappa B, and neuronal apoptosis in the epileptic rat brain*★

BACKGROUND：It has been reported that Ganoderma lucidum spore powder, a very well known Chinese traditional medicine, can affect immunoregulation, free radical scavenging, and anti-hypoxia responses. OBJECTIVE： To investigate the effect of Ganoderma lucidum spore powder on expression of insulin-like growth factor-1 （IGF-1）, nuclear factor-κB （NF-κB） and neuronal apoptosis in rats with pentylenetetrazol （PTZ）-induced epilepsy. DESIGN, TIME AND SETTING： A cellular and molecular biology experiment with randomized controlled study design was performed at the Central Laboratory of Basic Medical College of Jiamusi University from June to August 2005. MATERIALS： Thirty healthy, adult, male, Wistar rats were selected and randomly divided into 3 groups （10 rats per group）： control, epilepsy model, and Ganoderma lucidum spore powder. A sub-eclampsia PTZ dose （35 mg/kg） was intraperitoneally injected to induce epilepsy in the latter two groups. Wild Ganoderma lucidum spore powder （30 g/L） was provided by the wild Ganoderma lucidum plant nursery at Jiamusi, China. Immunohistochemical detection and terminal deoxynucleotidyl transferase-mediate dUTP nick end-labeling （TUNEL） kits were purchased from Wuhan Boster Biological Technology Co., Ltd., China. METHODS： Ganoderma lucidum spore powder was intragastrically administered at a dose of 10.0 mL/kg, once a day for 28 days. In the epilepsy and control groups, an equivalent volume of normal saline was intragastrically administered. MAIN OUTCOME MEASURES： Immunoreactivity for IGF-1 and NF-κB/P65 were detected by immunohistochemical staining. Neuronal apoptosis was detected using TUNEL methods. RESULTS： The hippocampus and cerebral cortex of rats with PTZ-induced epilepsy exhibited a higher number of apoptotic cells at high magnification （×400）, compared with the control group. Expression of IGF-1 and NF-κB were higher in the epilepsy group, compared with the control group （P 〈 0.01）. In Ganoderma lucidum spore-treated rats,     

Effect of bilobalide B on cholinergic hippocampal neurons exposed to cholesterol and apolipoprotein E4*☆

BACKGROUND： Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer＇s disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons. OBJECTIVE： To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4 DESIGN, TIME AND SETTING： This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006. MATERIALS： Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5 g were selected for this study. Cholesterol and apolipoprotein E4 （apoE4） were purchased from Sigma Company （USA）, bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312. METHODS： Hippocampal neurons were divided into three groups： a normal control group （routinely added media）, a model group （exposed to media containing 40 mg/L cholesterol and 30 mg/L apoE4 for 24 hours） and a bilobalide B group （exposed to media containing 160 mg/L bilobalide B for 16 hours, and then with addition of 40 mg/L cholesterol and 30 mg/L apoE4 for an additional 24 hours）. MAIN OUTCOME MEASURES： Levels of acetylcholine （ACh） and activity of acetylcholinesterase （ACHE） and choline acetyltransferase （CHAT） in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively. RESULTS： The ACh level was significantly lower in the model group than that in the normal control group （P 〈 0.01）, while it was markedly higher in the bilobalide B group than in the model group （P 〈 0.05）. Activity of AChE was significantly decreased in the model group compared with the normal control group （P 〈 0.05）. However, there was no significant difference between the model group and the bilobalide B group ?     

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     

精神分裂症阴性症状发病机制及治疗的研究进展

精神分裂症分为阳性症状和阴性症状,目前多数药物对于阳性症状的治疗疗效明显好于阴性症状的疗效.临床上,阴性症状主要是指正常的心理功能的消失或下降,如意志力减弱,内向孤僻,言语思维贫乏,冷漠,是最难消除的精神分裂症症状,甚至某些药物治疗可加重阴性症状.目前研究已发现多个神经递质可能参与了精神分裂症阴性症状的发病过程,如多巴胺（DA）受体、去甲肾上腺素、5-羟色胺（5-HT）受体等,同时还有很多非神经递质类因素与阴性症状有关.现将精神分裂症阴性症状的可能发病机制和治疗进展逐一阐述.     

氧化应激与认知功能障碍的研究进展

氧化应激（Oxidative Stress）不仅在糖尿病、高血压病等身心疾病中起着重要作用,而且对阿尔茨海默病（AlzheimerDisease,AD）、帕金森病（Parkin-son Disease,PD）等神经精神障碍的认知功能也有一定影响。强烈或持续性的氧化应激可通过诱导细胞凋亡和炎性反应导致细胞、组织损害。流行病学及动物研究均表明,母孕期遭受应激可能会影响胎儿的神经心理发育过程,造成胎儿大脑某区域的缺陷,引起持续性认知改变、神经内分泌和行为反应,增加后代精神疾病的患病风险。现对氧化应激与认知功能障碍的机制进行综述。