Objective To describe the spatial and temporal characteristics of neurofibrillary tangles (NFT) in brains of patients with Niemann-Pick disease type C (NPC). Methods In order to analyze formation of NFT in NPC, the brains collected from 17 patients with NPC aged from 7 months to 55 years old were investigated using antibodies against the protein tau and the specific proteins in mitotic phase. Results Typical NFT could be detected in the parahippocampns of a NPC patient as early as at 4 years old. The number of NFT were increasing along with the time. Gradually, the hippocampus and other regions of the temporal lobes and the frontal lobes would be affected with the time. Immunohistochemically, the NFT formed the shape similar to NFT seen in AD brains, without the presence of senile plagues. Interestingly,mitosis-phase markers appeared in the degenerating NPC neurons prior to hyperphesphorylation of tau and formation of NFT. Conclusions The formation of NFT does not result from aging, for there is no close relation between the presence of senile plagues and the formation of NFT. Ectopic activation of cdc2/cyclinB1 kinase complex might be an early event leading to NFT formation. Antagonist of the kinase complex may potentially slow down the formation of NFT.

Objective To study the offactory function test in Parkinson' s disease(PD), in order to promote the diagnosis of the PD. Methods Subjects included 95 middle-aged volunteers and 37 Pdpatients. A subjective olfactometry with T&T olfactometer was performed in all volunteers and patients.Olfactory event related potentials with isoamyl acetate were obtained in all volunteers and patients. Results The T&T olfactometer Results for the 2 sides were 4.6±1.1,4.4±1.2 in PD patients older than 70 years old and 3.9±1.7, 4.0±1.7 in those, respectively; while the data were 0.4±0.9,0.4±0.9 in volunteers older than 70 years, were 0.5±0.8,0.5±0.8 younger than 70 years old. There was a significant differencein T&T olfactometer Results between PD and volunteers (t=15.246,15.378,8.664,8.776, P<0.01). TheP2 latencies were respectively (734.9±143.2), (696.1±165.9) ms for the 2 sides in PD older than 70years, and (730.5±159.4), (719.5±159.2) ms in PD younger than 70 years;while they were (547.9±65.0), (558.5±56.3) ms, and (523.3±61.9), (526.8±62.0) ms in volunteers younger than 70 years.There was a significant difference in P2 latency between PD and volunteers (t = -3.940, -3.750,- 7. 514, - 8.205,P<0.01). Conclusions Olfactory dysfunction is an important index in PD. Olfactory function test is an useful method in the diagnosis of PD.

Objective To describe the prevalence and neuropsychological character of mild cognitive impairment (MCI) associated with Parkinson' s disease(PD-MCI). Methods One hundred and three PD patients and a control group of 32 healthy old subjects were chosen. Psychometric assessment included the Mini Mental State Examination, the Dementia Rating Scale and a series of neuropsychol ogicaltests. The Hamilton Rating Scale of Depression was used to assess depression in PD patients. Results (1)Twenty-one (20.4%) PD patients was diagnosed with dementia, 45 (43.7%) had a MCI and only 37(35.9%) had no cognitive impairment; (2) Subjects with PD-MCI were older, had a later onset of the PD,and displayed more severe motor symptoms compared with those without cognitive impairment; (3) The prevalence and neuropsychological profile of PD-MCI were thought to correlate with the dominating side and subtype of Parkinsonian symptoms, for patients with left-sided dominant symptoms had a significantly higher chance of suffering MCI than those with right-sided dominant symptoms, the ratio being 74.2% vs 42.2%,χ<'2 =7. 589,P <0.05; The tremor-dominant group took less time than the mixed group for Stroop word test measurement ((80.8±39.9) s vs (94.4±30.0) s,t=3.332,P<0.01). Conclusion Identification of MCI is of important clinical significance, which helps to treat patients differently and thus predict the prognosis.

Objective To study the efficacy of entacapone for motor fluctuations in Parkinson's disease. Methods Pubmed, Embase, Cochrane Database were searched for randomized controlled trial studies (RCTs) on entacapone compared to placebo in the treatment of Parkinson' s disease with motor fluctuations. Data were extracted and evaluated by two reviewers independently with designed extractian form. Revman 4. 2. 10 software was used for data analysis. Results Ten RCTs involving 2212 patients were included. The Results showed that entaeapone tends to increase "on" time, decrease "off" time and daily levodopa dosage (WMD=-1.41,95% CI -2. 09- -0.72) and improve "on" time motor symptoms and the quality of life. But it might increase the rate of dyskinesia (OR=2.00, 95% CI 1.55-2.58).Conclusion The systematic review indicates that entaeapone might be an effective agent for parkinsonian patients with motor fluctuations and more high quality RCTs with the same effect measures are required.

Objective To investigate the mechanism of P/Q-type calcium channel in nitroglycerin induced migraine experimental model Methods Twenty Sprague-Dawley rats ( half female and half male) were randomly divided into control group and model group. The model of migraine rats was reproduced using Tasserelli Cristina method that wassubcutaneou injection of GTN of 10 mg/kg, once a week for four weeks. After the model of migraine had been established, trigeminal ganglion and trigeminocervical complex and cortex of frontal lobe were removed and the expressions of P/Q-type calcium channel were detected by RT- PCR and Western-blot, and at the same time the concentration of intracellular Ca2+ was investigated by Fluo- 3/AM fluorometric method. Results Compared with the control group, the expression of mRNA and protein of P/Q-type calcium channel of trigeminal ganglion and trigeminocervical complex (mRNA: 0. 472 36± 0. 049 54; protein: 0. 337 25 ± 0. 035 93 ) and cortex of frontal lobe ( mRNA: 0. 547 45 ± 0. 044 39 ; protein : 0. 402 13 ± 0. 029 83) in model group all upregulated (t = 2. 6697, 3. 1993, 3. 4398 and 3. 7661, all P <0. 05), at the same time the concentration of intracellular Ca2+ in model group increased (211 182 ± 12 973 vs 135 243 ± 18 105 in trigeminal ganglion and trigeminocervical complex; 186 511 ± 18 297 vs 143 289±25 175 in cortex of frontal lobe. t =10.7819 and 4. 3917, beth P<0.05). Conclusions P/Q- type calcium channel may play a role in the pathogenesis of migraine via its upregulated expression.

Objective To investigate how functional connectivity changes within default-mode network related to posterior cingulated cortex employing resting-state functional MRI (tMRI). Methods fMRI was compared between 16 mild Alzheimer' s disease (AD) patients and 16 normal elder subjects. Regions of functional connectivity to posterior cingulated cortex were gathered by calculating temporal correlations in low frequency fMRI signal fluctuations. SPM2 was applied to calculate significant differences of connectivity between group and within group. Significance threshold was set up at the corrected P <0. 01, pixel extent > 5. A random effect two-example t test was performed by SPM2 to achieve significant difference of functional connection between groups ( P < 0. 01, corrected, t = 2. 47, pixel extent > 5 ). Results Regions showing disrupted connectivity to posterior cingulated cortex were: ventral medial prefrontal cortex (MPFC), bilateral visual cortex, infero-temporal cortex (ITC), and left hippocampus, right thalamus, right dorsal-lateral prefrontal cortex ( DLPFC), and precuneus. There were also regions showing increased connectivity with leftward asymmetry, these regions included: MPFC, left ITC, bilateral DLPFC, left pre- central motor cortex and left basal ganglia. Conclusions Impairments of memory and high visual-related functions in AD can be explained by functional disconnection in resting-state. Remoldability is reserved in mild AD to compensate for brain function which is taxed by left hemisphere preferentially. Our findings suggest that resting-state fMRI might be an appropriate approach for evaluating AD brain mechanism.

Objective To investigate the clinical manifestions, pathological features and diagnosing methods of Lafora disease. Methods The chnical and pathological features of 5 patients with Lafora disease who were diagnosed by axillary biopsies were systemically studied. The specimen were stained by HE, PAS and AB-PAS methods. Results Four of 5 cases had an onset during adolescence and 1 during adulthood. All cases presented with progressive generalized tonic-clonic seizure, myoclonus and dementia. Emotional disturbance, dysarthria and ataxia appeared in the early course of the disease. Lafora bodys were identified in myoepithelial cells and duct cells of both eccrine sweat glands and apecrine sweat glands in the biopsies of axillary skin. Conclusions Lafora disease could be confirmed by round and oval periodic acid-Schiff- positive inclusions in skin biopsy specimen combined with the proper clinical settings. Both axillary and other skins can be chosen as the sites of biopsy.

Objective To analyze the clinical features of 27 Chinese patients with Kennedy's disease(KD), a sex-linked inheritance disorder. Methods We collected the clinical data of 27 KD patients whose diagnosis were confirmed by gene examination to analyze their clinical features, as well as their serum levels of sex hormones and biochemical indicators. Results Patients with spinal and bulhar muscular atrophy tend to have an adult onset, exhibiting a slow progression of lower motor neuronal weakness and atrophy involving limbs and bulbar zones. Part of the invalids presented signs of androgen insensitivity such as gynecomastia or reduced sexual function, even though their degrees of sex hormones were normal. There was mild motor functional lesion which correlated with the course of the disease ( r = 0. 77, P = 0. 000). The degrees of creatine kinase ( ( 920. 10 ± 495.54 ) U/L ) and triglyceride ( ( 3.27 ± 2. 78) mmool/L) increased mildly and was significantly different from the levels of healthy ones (107.20 U/L,t =7.517,P =0.000;1.40 mmol/L, t =2.687,P =0.017). Conclusions Basically, Chinese KD patients present the same clinical features as the literature reports, however they have distinctive aspects such as elevated degree of triglyceride. The present research can help us to understand the features of Chinese KD more particularly.

Objective To investigate the anti-inflammatory impacts of in the progression of Alzheimer' s disease (AD) in the rat model induced by β-amyloid 1-42 (Aβ1-42 ). Methods Sixty healthy male Wistar rats (weight 250--300 g) were randomly divided into 4 groups: control group, model group, statins control group and statins treatment group, 15 in each group. Rats model were established via intracerebroventricular injection of A13, and then atorvastatin (5 mg·kg-1·d-1) were given to the treatment group for 3 weeks, saline to the control group. Water Maze was used to observe learning and memory ability changes in rats, and expression of inflammatory eytokines IL-1β, IL-6 and TNF-α in the hippocampus were repectively detected by immunohistochemical technique. Furthermore, HE staining patterns, hippoeampns neurons and glial cells in the small ultra structural changes were observed under light microscope and electron microscope respectively. Results The model rats resulted in decreased learning and memory abihties ( the escaping latency: 12. 0 ± 1.2, 41.3 ± 3.4, t = 18. 0363, P < 0. 01 ) and increased secretion of the brain inflammatory factor compared with the controls with statistically significant difference (IL-1β:53.5 ± 2.4, 101.0 ± 3. 8, t = 23. 8246, P < 0. 01 ). Atorvastatin treatment group improved learning and memory performance ( the escaping latency: 25. 7 ± 1.6, 41.3 ± 3.4, t = 9. 1076, P < 0. 01 ), reduced the secretion of inflammatory factors in the hippocampus, compared with the model rats (IL-1β:60.0±3.4,101.0±3.8, t = 18.0231, P <0.01). There were less injured nerve cells and proliferated glial cells in the atorvastatin treatment group than in the model group. Conclusions Atorvastatin plays an anti-inflammatory role in the progression of Alzheimer's disease, reducing the nerve cell damage and improving learning and memory ability.

Objective To investigate the effect of diabetes on the expression of the glucose transporter (GLUT-1) in blood brain barrier (BBB) endothelial cell at different time points. Methods Forty male SD rats were randomly divided into normal control and diabetic group. Diabetic model of SD rats was established by intravenous streptozotocin(50 mg/kg) injection. Ten rats in each group were sacrificed on the 2nd month and 10th month respectively. The rat' s prefrontal cortex was removed to observe the expression of GLUT-1 in BBB EC with immunohistochemical(IHC) staining. Results By IHC method, the number of GLUT-1 positive microvessels was significantly decreased in diabetic group in the 2nd month (4. 3 ± 0. 9) compared with that of control group (6.4 ± 1.7, t = 7. 586, P < 0. 01 ) ; the number of GLUT-1 positive microvessels was significantly increased in the diabetic group in the 10th month (8.4 ± 1.4) compared with that of control group (5. 8 ± 1.7, t = 15.922,P < 0. 01 ). Conclusions Short-term diabetes GLUT-1 expression in BBB EC is downregulated in early stage, while it is upregulated in advanced stage.