Correlation of SV2C rs1423099 single nucleotide polymorphism with sporadic Parkinson's disease in Han population in Southern China.

BACKGROUND: The synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction. OBJECTIVE: This study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson's disease (PD) in the Chinese Han population. MATERIALS AND METHODS: This study enrolled 351 patients with sporadic PD and 240 normal controls in Chinese Han population. Peripheral blood DNA was extracted by DNA extraction kits and the rs1423099 genotype was analyzed by Agena MassARRAY DNA mass spectrometry. The differences in genotype and allele distribution frequencies between PD patients and control groups were compared using chi-squared tests or Fisher's exact tests. RESULTS: No statistical difference was revealed in age and sex distribution between the cases and control groups, and the distribution of genotype and allele frequencies was consistent with the Hardy-Weinberg equilibrium test. In SV2C rs1423099 dominant model, the frequency of the CC/CT genotype was significantly higher in the PD group compared to the control group (OR = 4.065,95% CI: 2.801-10.870, p = 0.002). Nevertheless, in the recessive model, CC or CT/TT genotypes have no statistical difference in the two groups (p = 0.09). Additionally, in allelic analysis, the C allele was investigated to increase the risk of PD (OR = 1.346, 95% CI: 1.036-1.745, p = 0.026); Furthermore, subgroup analysis suggested that those carrying the C allele in the male subgroup were at a higher risk to afflicted with PD (OR = 1.637, 95% CI: 1.147-2.336, p = 0.006). CONCLUSION: SV2C rs1423099 single nucleotide polymorphism was associated with sporadic Parkinson's disease in the Chinese Han population, particularly in males.

Parkinson's disease in a patient with GBA and LRRK2 covariants after acute hypoxic insult: a case report.

BACKGROUND: The glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) genes are associated with the risk of sporadic Parkinson's disease (PD). As an environmental factor, hypoxic insults may impair dopamine neurons in the substantia nigra and exacerbate PD symptoms. However, covariants of GBA and LRRK2 combined with hypoxic insults in clinical cases of Parkinsonism have not yet been reported. CASE PRESENTATION: A 69-year-old male patient with PD and his relatives were clinically characterized and sequenced using the whole-exome technique. A novel covariant, c.1448 T > C (p. L483P, rs421016) on GBA and c.691 T > C (p. S231P, rs201332859) on LRRK2 were identified in this patient who first developed bradykinesia and rigidity in the neck at one month after an acute hypoxic insult during mountaineering. The patient presented with a mask-like face, festinating gait, asymmetric bradykinesia, and moderate rigidity. These symptoms were treated with levodopa and pramipexole, resulting in a 65% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. These parkinsonian symptoms persisted and developed with hallucinations, constipation, and rapid eye movement sleep behavior disorder. After 4 years, the patient exhibited a wearing-off phenomenon and died from pulmonary infection 8 years after disease onset. His parents, wife, and siblings were not diagnosed with PD, and his son carried p. L483P without Parkinsonism-like symptoms. CONCLUSIONS: This is a case report of PD after hypoxic insult in a patient carrying a covariant of GBA and LRRK2. This study may help us understand the interaction between genetic and environmental factors in clinical PD.

In-Hospital Emergency Treatment Delay Among Chinese Patients with Acute Ischaemic Stroke: Relation to Hospital Arrivals and Implications for Triage Pathways.

Introduction: Timely access to emergency treatment during in-hospital care phase is critical for managing the onset of acute ischaemic stroke (AIS), particularly in developing countries. We aimed to explore in-hospital emergency treatment delay and the relation of door-to-needle (DTN) time to ambulance arrivals vs walk-in arrivals. Methods: Data were collected from 1276 Chinese AIS patients admitted to a general, tertiary-level hospital for intravenous thrombolysis. Information on patients' characteristics and time taken during in-hospital emergency treatment was retrieved from the hospital registry data and medical records. Ambulance arrival was defined as being transported by emergency ambulance services, while walk-in arrival was defined as arriving at hospital by regular vehicle. In-hospital emergency treatment delay occurred when the DTN time exceeded 60 minutes. We performed multivariable logistic regression analysis to explore the association between hospital arrivals (by ambulance vs by walk-in) and treatment delay after adjustment for age, sex, education, marital status, residence, medical insurance, number of symptoms, clinical severity and survival outcome. Results: Over half (53.76%) of patients aged over 60 years. Around one-fifth (20.61%) of patients admitted to hospital through emergency ambulance services, while their counterparts arrived by regular vehicle. Overall, the median time taken from the hospital door to treatment initiation was 86.0 minutes. Patients arrived by ambulance (adjusted odds ratio [aOR] = 1.744, 95% confidence interval [CI] = 1.185-2.566, p = 0.005), had higher socio-economic status (aOR = 1.821, 95% CI = 1.251-2.650; p = 0.002), or paid out-of-pocket (aOR = 2.323, 95% CI = 1.764-3.060; p < 0.001) had an increased likelihood of in-hospital emergency treatment delays. Conclusion: In-hospital emergency treatment delay is common in China, and occurs throughout the entire emergency treatment journey. Having a triage pathway involving hospital arrival by ambulance seems to be more likely to experience in-hospital emergency treatment delay. Further efforts to improve triage pathways may require qualitative evidence on provider- and institutional-level factors associated with in-hospital emergency treatment delay.

A case of congenital afibrinogenemia with multiple thrombotic and hemorrhagic disorders.

This is a case of congenital afibrinogenemia with multiple thrombotic and hemorrhagic events. His fibrinogen concentration was negatively correlated with thrombin time and prothrombin time and abnormally negatively correlated with plasma D-dimer levels. The individualized standard for fibrinogen concentration may help to balance thrombotic and hemorrhagic events for this disease.

CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear. METHODS: Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo. RESULTS: We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP+-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS. CONCLUSION: This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.

Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson's Disease.

Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor exclusively expressed in the central nervous system (CNS). It contributes to abnormal protein aggregation in neurodegenerative disorders, but its role in Parkinson's disease (PD) is still unclear. Methods: In this case-control study, we measured the concentration of the soluble fragment of TREM2 (sTREM2) in PD patients, evaluated their sleep conditions by the PD sleep scale (PDSS), and analyzed the relationship between sTREM2 and PD symptoms. Results: We recruited 80 sporadic PD patients and 65 healthy controls without disease-related variants in TREM2. The concentration of sTREM2 in the CSF was significantly higher in PD patients than in healthy controls (p < 0.01). In the PD group, the concentration of sTREM2 had a positive correlation with α-syn in the CSF (Pearson r = 0.248, p = 0.027). Receiver operating characteristic curve (ROC) analyses showed that sTREM2 in the CSF had a significant diagnostic value for PD (AUC, 0.791; 95% CI, 0.711-0.871, p < 0.05). The subgroup analysis showed that PD patients with sleep disorders had a significantly higher concentration of sTREM2 in their CSF (p < 0.01). The concentration of sTREM2 in the CSF had a negative correlation with the PDSS score in PD patients (Pearson r = -0.555, p < 0.01). The ROC analyses showed that sTREM2 in the CSF had a significant diagnostic value for sleep disorders in PD (AUC, 0.733; 95% CI, 0.619-0.846, p < 0.05). Conclusion: Our findings suggest that CSF sTREM2 may be a potential biomarker for PD and it could help predict sleep disorders in PD patients, but multicenter prospective studies with more participants are still needed to confirm its diagnostic value in future.

Bone-Derived Factors as Potential Biomarkers for Parkinson's Disease.

Background: Parkinson's disease (PD) and osteoporosis are both common aging diseases. It is reported that PD has a close relationship with osteoporosis and bone secretory proteins may be involved in disease progression. Objectives: To detect the bone-derived factors in plasma and cerebrospinal fluid (CSF) of patients with PD and evaluate their correlations with C-reaction protein (CRP) level, motor impairment, and Hoehn-Yahr (HY) stage of the disease. Methods: We included 250 PD patients and 250 controls. Levels of osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), Sclerostin (SO), Bone morphogenetic protein 2 (BMP2), and Dickkopf-1 (DKK-1) in plasma and CSF were measured by custom protein antibody arrays. Data were analyzed using Mann-Whitney U-test and Spearman's receptor activator of NF-κB (RANK) correlation. Results: Plasma levels of OCN and OPN were correlated with CRP levels and HY stage and motor impairment of PD. Furthermore, the plasma assessment with CSF detection may enhance their potential prediction on PD. Conclusions: OCN and OPN may serve as potential biomarkers for PD. The inflammation response may be involved in the cross-talk between the two factors and PD.

Association of ADAM10 gene variants with sporadic Parkinson's disease in Chinese Han population.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Genetic factors play important roles in PD risk. rs653765 and rs514049 of ADAM10 were reported to be associated with Alzheimer's disease (AD) in Caucasian population; however, the association of the two variants with PD in Chinese Han population remains unknown. The present investigation aimed to explore the possible association of ADAM10 variants with PD in Chinese Han population. METHODS: We enrolled 565 PD patients and 518 healthy controls to conduct a case-control study. DNA samples were extracted from peripheral blood leukocytes, and the genotypes were determined by utilization of MassARRAY platform. Plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found CC genotype of rs514049 was associated with an increased risk of PD (OR (95% CI) = 3.776 (1.127-11.217), p = 0.018). The C allele frequency of rs514049 was significantly higher in PD group (OR (95% CI) = 1.328 (1.031-1.709), p = 0.028), especially in male subgroup (OR (95% CI) = 1.484 (1.053-2.092), p = 0.024). However, there was no significant difference in the genotype or allele frequencies for rs653765 within the groups. Plasma levels were significantly decreased in PD patients compared with controls (p < 0.001). CONCLUSIONS: Our data suggested that C allele of rs514049 in ADAM10 may increase the risk of PD in Chinese Han population, especially in males. The decreased plasma levels are probably involved in PD development.

Analysis of Cerebrospinal Fluid Soluble TREM2 and Polymorphisms in Sporadic Parkinson's Disease in a Chinese Population.

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that mediates the degradation disorder of amyloid ß (Aß) in Alzheimer's disease. However, the role of TREM2 in Parkinson's disease (PD) and α-Synclein (α-Syn) degradation is largely unknown. METHODS: In this case-control study on Chinese population, we sequenced for polymorphisms in exon 2 of the TREM2 gene in 1,292 individuals, PD cases (n = 612), healthy controls (n = 680) by Sanger sequence, and compared the distribution of allelic frequencies between the two groups by the Fisher's exact test. Additionally, we developed and used the enzyme-linked immunosorbent assay to evaluated soluble TREM2 (sTREM2) levels in the cerebrospinal fluid (CSF), and plasma in partial of sequenced groups (55 PD and 40 healthy controls) analyzed their relationship with total a-syn (t-a-Syn). RESULTS: Two novel variants were detected in exon 2 of the TREM2 gene, namely, p.S81 N, p.G58D; however, these were not significantly associated with PD (612 PD and 680 healthy controls). sTREM2 in CSF was significantly upregulated in PD patients compared to healthy controls (433.1 ± 24.7 pg/mL vs. 275.2 ± 17.9 pg/mL, p < 0.0001), but not in plasma (281.7 ± 29.3 pg/mL vs. 257.8 ± 16.5 pg/mL, p = 0.805). In PD patients, sTREM2 was positively correlated with t-α-syn (r = 0.62, p = 0.0001) in CSF, but not in plasma (r = 0.02, p = 0.89). CONCLUSIONS: Although it may not indicate that exon 2 polymorphisms of TREM2 play a role in the pathogenesis of PD in the Chinese population, our findings described above highlight the relevance of CSF sTREM2 as a promising biomarker and are extremely possible to the therapeutic target for PD in the future.

Relationship between variants of 17 newly loci and Parkinson's disease in a Chinese population.

Genetic factors play significant roles in the causes of Parkinson's disease (PD). Recently, a meta-analysis of genome-wide association study (GWAS) has identified 17 loci associated with PD. The objective of our study was to investigate the association of 17 single-nucleotide polymorphisms with the risk of PD in Chinese population. We performed a case-control association study, and 1189 subjects comprising 652 PD patients and 537 controls were genotyped by using a Mass ARRAY System or a TaqMan assay. We found that rs601999 (OR (95% CI) = 3.378 (2.273-5.051), p < 0.001), rs11343 (OR (95% CI) = 0.426 (0.210-0.862), p = 0.018), rs353116 (OR (95% CI) = 0.738 (0.577-0.943), p = 0.015), and rs2280104 (OR (95% CI) = 1.371 (1.078-1.743), p = 0.010) were significantly associated with PD in Chinese population. However, no significant association was found in the remaining 13 single-nucleotide polymorphisms between both groups.

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo.

BACKGROUND: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (ß5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. METHODS: In this study, we investigated the role of ß5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. RESULTS: We showed that 6-OHDA upregulated ß5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of ß5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of ß5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA. ß5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons. CONCLUSION: Taken together, our data suggest that ß5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

Iron promotes α-synuclein aggregation and transmission by inhibiting TFEB-mediated autophagosome-lysosome fusion.

Recent studies have strongly shown that cell-to-cell transmission of neuropathogenic proteins is a common mechanism for the development of neurodegenerative diseases. However, the underlying cause is complex and little is known. Although distinct processes are involved in the pathogenesis of various diseases, they all share the common feature of iron accumulation, an attribute that is particularly prominent in synucleinopathies. However, whether iron is a cofactor in facilitating the spread of α-synuclein remains unclear. Here, we constructed a cell-to-cell transmission model of α-synuclein using SN4741 cell line based on adenovirus vectors. Cells were treated with FeCl2, and α-synuclein aggregation and transmission were then evaluated. In addition, the possible mechanisms were investigated through gene knockdown or over-expression. Our results demonstrated that iron promoted α-synuclein aggregation and transmission by inhibiting autophagosome-lysosome fusion. Furthermore, iron decreased the expression of nuclear transcription factor EB (TFEB), a master transcriptional regulator of autophagosome-lysosome fusion, and inhibited its nuclear translocation through activating AKT/mTORC1 signaling. After silencing TFEB, ratios of α-synuclein aggregation and transmission were not significantly altered by the presence of iron; on the other hand, when TFEB was over-expressed, the transmission of α-synuclein induced by iron was obviously reversed; suggesting the mechanism by which iron promotes α-synuclein transmission may be mediated by TFEB. Taken together, our data reveal a previously unknown relationship between iron and α-synuclein, and identify TFEB as not only a potential target for preventing α-synuclein transmission, but also a critical factor for iron-induced α-synuclein aggregation and transmission. Indeed, this newly discovered role of iron and TFEB in synucleinopathies may provide novel targets for developing therapeutic strategies to prevent α-synuclein transmission in Parkinson's disease.

Association of DNMT3b gene variants with sporadic Parkinson's disease in a Chinese Han population.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Epigenetic modifications, specifically DNA methylation, have been implicated in the development of this disease. Genetic variants of DNA methyltransferase 3b (DNMT3b), one of the most important DNA methyltransferases, were shown to be associated with PD in a Brazilian population. However, it is unclear whether genetic variants of DNMT3b increase the risk of PD in the Chinese Han people. The present study aimed to investigate the association of the DNMT3b variants rs2424913, rs998382 and rs2424932 with PD in a Chinese Han population. METHODS: We studied 487 Chinese Han patients with sporadic PD and 485 healthy age-, sex- and ethnicity-matched controls. DNA was extracted from peripheral blood leukocytes and the individual genotypes were determined using the SNaPshot method. RESULTS: We found that the rs2424932 and rs998382 variants were significantly associated with an increased risk of PD compared to the controls [rs2424932: odds ratio (OR) = 1.632, 95% confidence interval (CI) = 1.108-2.406, p = 0.013; rs998382: OR = 1.612, 95% CI = 1.103-2.382, p = 0.014]. Subgroup analysis suggested that female patients carrying the rs2424932 or rs998382 variants were more likely to develop PD than female controls (rs2424932: OR = 3.863, 95% CI = 2.004-7.445, p < 0.001; rs998382: OR = 3.679, 95% CI = 1.943-6.964, p < 0.001). Haplotype analysis indicated that the three variants comprised one block and that the Trs2424913 -Crs998382 -A rs2424932 haplotype was correlated with an increased risk of PD (p = 0.0046), especially for Chinese Han females (p < 0.0001). CONCLUSIONS: The results of the present study strongly suggest that DNMT3b variants are associated with PD in the Chinese Han people, especially females.

Peripheral Lymphocyte Subsets as a Marker of Parkinson's Disease in a Chinese Population.

In this study, we conducted a clinical analysis of lymphocyte subtypes in 268 patients with Parkinson's disease (PD) to assess their clinical impact as a potential marker of advanced PD in Chinese patients. The participants comprised 268 sporadic PD patients and 268 healthy controls. The numbers of natural killer (NK) cells and CD3+, CD3+CD4+, CD3+CD8+, and CD19+ lymphocytes from peripheral blood were determined by immunostaining and flow cytometric analysis and the percentages of these CD+ T cells were calculated. The ratio of regulatory T (Treg)/helper T 17 (Th17) lymphocytes from 64 PD patients and 46 controls was determined by flow cytometric analysis. The results showed that the percentage of NK cells was higher in advanced PD patients than in controls (22.92% ± 10.08% versus 19.76% ± 10.09%, P = 0.006), while CD3+ T cells are decreased (62.93% ± 9.27% versus 65.75% ± 9.13%, P = 0.005). The percentage of CD19+ B cells in male patients was lower (P = 0.021) than in female patients, whereas NK cells were increased (P < 0.0001). The scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and the Non-Motor Symptoms Scale in late-onset PD patients were significantly higher than those in early-onset patients (P = 0.024 and P = 0.007, respectively). The percentage of CD19+ B cells in patients with UPDRS scores >24 was lower than in those with scores <24 (10.17% ± 4.19% versus 12.22% ± 5.39%, P = 0.009). In addition, the Treg/Th17 ratio in female patients was higher than that in female controls (13.88 ± 6.32 versus 9.94 ± 4.06, P = 0.042). These results suggest that the percentages of NK cells, CD3+ T cells, and CD19+ B cells along with the Treg/Th17 ratio in peripheral blood may be used to predict the risk of PD in Chinese individuals and provide fresh avenues for novel diagnostic biomarkers and therapeutic designs.

Association analysis of HLA-DRA in Chinese patients with sporadic Parkinson's disease.

Our aim is to explore the linkage between single nucleotide polymorphisms (SNPs) in human leukocyte antigen (HLA)-DRA and Parkinson's disease (PD). 542 sporadic PD patients and 674 healthy controls were recruited to investigate this association in the Chinese population by the screening of 15 SNPs in HLA-DRA, and the association of rs3129882 was further re-evaluated by performing meta-analysis and meta-regression analysis. No SNPs in HLA-DRA were significantly associated with PD in the Chinese patients. Although the rs3129882 allele-G frequency in the Caucasian population was lower than that in Chinese population, meta-analysis showed no association of rs3129882 allele-G with PD in the Chinese or Caucasian population. In consideration of the heterogeneity (I(2)=78.6%, Q=66.33, p<0.000), subgroup analysis was performed, revealing a significant association between rs3129882 and PD in the Caucasian patients from the genome-wide association studies (OR=1.22, 95% CI: 1.16, 1.27); however, this association was not consistently observed in the studies performed using other DNA sequencing techniques. Meta-regression analysis, which accounted for 58.3% of the heterogeneity, revealed that the impact of the sequencing technique used was significant (p=0.027) compared with ethnicity. Regression analysis of the Caucasian population further showed that the sequencing technique used contributed to 71.2% of the heterogeneity (p=0.033). Our data support the absence of a linkage between the risk loci in HLA-DRA and PD in Chinese patients. The different DNA sequencing techniques used in PD studies may largely account for the controversial conclusions concerning rs3129882.

Neuroprotection by platelet-activating factor acetylhydrolase in a mouse model of transient cerebral ischemia.

Neuronal damage after transient cerebral ischemia is exacerbated by signaling pathways involving activated platelet-activating factor (PAF) and ameliorated by PAF-acetylhydrolase (PAF-AH); but whether cerebral neurons can be rescued by human recombinant PAF-AH (rPAF-AH) remains unknown. Adult male mice underwent a 60 min middle cerebral artery occlusion (MCAO) and reperfusion for 24h. Then, the mice received intravenous tail injections with different drugs. Neurological behavioral function was evaluated by Bederson's test, and cerebral infarction volume was assessed with tetrazolium chloride (TTC) staining. mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2, collagenase-1), MMP-9 (gelatinase-B), and vascular endothelial growth factor (VEGF) were determined by quantitative real-time PCR (RT-PCR) and western blot analysis, respectively. Compared with the vehicle group, rPAF-AH significantly improved sensorimotor function (42%, P=0.0001). The volume of non-infarcted brain tissue was increased by the rPAF-AH treatment (16.3±4.6% vs. 46.0±10.3%, respectively). rPAF-AH significantly reduced mRNA and protein levels of MMP-2 and MMP-9, but increased the mRNA (P<0.001) and protein levels (P<0.01) of VEGF. These results demonstrate that rPAF-AH provides neuroprotection against ischemic injury. Neuroprotection might be induced not only by decrease in MMP-2 and MMP-9 expression, but also by increased VEGF expression.

Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson's disease and multiple system atrophy.

UNLABELLED: We explored if magnetic resonance imaging sequences might aid in the clinical differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). We measured the volumes of the olfactory bulb, the olfactory tract, and olfaction-associated cortical gray matter in 20 IPD patients, 14 MSA patients, and 12 normal subjects, using high-resolution magnetic resonance imaging sequences in combination with voxel-based statistical analysis. We found that, compared to normal subjects and MSA patients, the volumes of the olfactory bulb and tract were significantly reduced in IPD patients. The gray matter volume of IPD patients decreased in the following order: the olfactory area to the right of the piriform cortex, the right amygdala, the left entorhinal cortex, and the left occipital lobe. Further, the total olfactory bulb volume of IPD patients was associated with the duration of disease. The entorhinal cortical gray matter volume was negatively associated with the UPDRS III score. CONCLUSION: Structural volumes measured by high-resolution magnetic resonance imaging may potentially be used for differential diagnosis of IPD from MSA.