Objective To investigate the optimal scan time of MRI using the imaging probe alphamethyl-L-tryptophan(α-MTrp)-superparamagnetic iron oxide nanoparticles (SPIONs) for localizing temporal lobe epilepsy (TLE) foci.Methods α-MTrp-SPIONs were injected into rat models of TLE through the tail vein during the acute and chronic stages (72 h and 8 weeks after status epilepticus,respectively).MRI was performed before and 1,2,4,8,24 h after the injection in all animals,and the T2 values of the epileptogenic regions were measured.One-way repeated measures analysis of variance was used for data analysis.Results Compared with the T2 values before the injection of α-MTrp-SPIONs,the T2 signal of epileptogenic regions after the injection had a negative increased change.The T2 values before and 1,2,4,8,24 h after the injection in acute stage were 112.08±5.85,107.83±6.59,105.08±6.79,95.58±5.14,100.92± 5.81,105.17±6.31 respectively,and those in chronic stage were 112.08±7.53,107.75±7.10,102.75± 5.50,96.17±5.01,97.75±4.37,102.92±4.74.The T2 values after the injection were significantly different from those before the injection (both P＜0.01).The T2 value at 4 h after the injection decreased mostly.Conclusions α-MTrp-SPIONs can precisely localize epileptogenic regions of TLE on MRI.The optimal scan time is 4 h after the injection.

Objective To determine the expression profile of serum microRNAs(miRNAs) in early-onset familial Alzheimer's disease (EO-FAD) patients. methods miRNA microarrays were performed to detect the expression profile of serum miRNAs in 2 cases of EO-FAD patients,2 cases of EO-FAD carriers and 2 cases of normal controls.Preliminary bioinformatic analysis was conducted. Result sIt was found that 21 miRNAs were up-regulated and 22 miRNAs were down-regulated in serum of EO-FAD patients,the differences were statistically significant(P<0.05).miR-5704(P=0.0002),miR-4639-3p(P=0.0195),miR-107(P=0.0204) were markedly up-regulated,miR-5572(P=0.0008),miR-204-3p(P=0.0014),miR-542-5p(P=0.0106) and miR-155-5p(P=0.0240) were markedly down-regulated.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the dysregulated miRNAs may be involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.Conclusion miR-5704,miR-4639-3p,miR-107,miR-5572,miR-204-3p,miR-542-5p and miR-155-5p may be used as potential biomarkers of EO-FAD,and involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.

Objective To investigate the phenotypes and genetics of an early-onset familial Alzheimer′s disease ( EO-FAD ) family.Methods The clinical manifestations , brain MRI results and neuropathological findings of the proband and pedigree members of the EO -FAD family were evaluated. Autopsy was performed in the proband . Results Fifteen members of this family had a presenilin 1 (PSEN1) p.G378E mutation and nine of them had clinical manifestations or the MRI changes of EO -FAD. Neuropathological findings from autopsy of the proband disclosed moderate cortical atrophy throughout the brain, especially in frontal lobe and temporal lobe .Neuronal loss with gliosis was observed in the cortices of the frontal, temporal and occipital lobes , as well as in parahippocampal gyrus .Numerous senile plaques and neurofibrillary tangles were present in the cerebral cortex .The proband′s younger sister showed similar clinical presentations and MRI changes , and other members of this family demonstrated progressive memory loss.Conclusion A p.G378E mutation in the PSENl gene was identified in a Chinese EO-FAD pedigree.

Objective To study the effect of anti-epileptic,nootropic drugs on the expression of NCAM and ERK2 in the hippocampus changes on the epileptic rats with cognitive dysfunction.Methods A total of 120Wistar rats were used.20 controls and 100 in which epilepticus with cognitive dysfunction were randomly assigned to 5 groups (n =20/group) that received daily treatments for 30 days with either (1) saline (epilepsy),(2) carbamazine (traditional anti-epileptic),(3) oxcarbazine (new anti-epileptic),(4) aniracetam (brain protective),or (5) donepezil (nootopic).Spatial learning and memory were assessed with a Morris Water Maze (MWM).Hippocampus tissue was assessed for NCAM1 and ERK-2 mRNAs by RT-PCR and proteins by immunochemistry.Results The mean escape latency of the place navigation test:EP group ((67.14 ± 7.37)s)was all higher than NS group (35.78 ± 4.84 s)and there was statistical significance (P ＜ 0.01),carbamazepine group ((81.23 ± 9.46)s) ＞ EP group((67.14 ±7.37)s) ＞ donepezi group((53.75 ±6.74) s) (P＜0.01).Immunohistochemical and RT-PCR result:carbamazepine ＜ oxcarbazepine ＜ epilepsy ＜ aniracetam ＜ donepezi group.Compared with control group,donepezil group ＞ control group (P ＜ 0.01),aniracetam group ＞ control group (P ＜ 0.05).Conclusion ERK-2 expression is decreased and NCAM 1 expression is increased in the hippocampus in the epileptic rats.Thus,both are involved in cognitive dysfunction.Carbamazepine aggravates cognitive dysfunction,whereas donepezil improves cognitive dysfunction associated with epilepsy.

INTRODUCTIONThe present study aimed to investigate the possible associations between serum levels of visfatin, an adipokine, and atherosclerosis in patients with ischaemic cerebrovascular disease.

METHODSA total of 95 participants were recruited for this study. Group A comprised 35 individuals with no history of cerebrovascular disease (control group) and Group B comprised 60 patients with ischaemic cerebrovascular disease. Group B was further categorised into two subgroups based on the ultrasonographic findings of the common carotid artery intima‑media thickness (CCA‑IMT) - Group B1 consisted of 21 patients with no atherosclerosis (i.e. CCA‑IMT ≤ 0.9 mm) and Group B2 consisted of 39 patients with atherosclerosis (i.e. CCA‑IMT > 0.9 mm). The body mass index, fasting blood total cholesterol, triglycerides, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol and glucose levels of each patient were measured. Serum visfatin levels were determined using enzyme‑linked immunosorbent assays. Visfatin levels were compared between groups, and stepwise logistic regression analysis was used to identify risk factors for atherosclerosis, including visfatin levels.

RESULTSThe mean serum visfatin level of the patients in Group B was higher than that in Group A (75.5 ± 77.80 ng/mL vs. 8.6 ± 4.69 ng/mL; p < 0.05) and the level was higher in patients from Group B2 than those from Group B1 (89.0 ± 80.68 ng/mL vs. 50.4 ± 72.44 ng/mL; p < 0.05). Multivariate regression analysis showed that CCA‑IMT values were not significantly associated with visfatin levels. However, logistic regression analysis showed that serum visfatin was an independent risk factor for atherosclerosis (odds ratio 37.80; p = 0.004).

CONCLUSIONSerum visfatin may be an independent risk factor for cerebral infarction, as high serum visfatin levels are positively associated with the underlying pathogenic mechanisms of ischaemic cerebrovascular disease.

Adipokines ; metabolism ; Adipose Tissue ; pathology ; Adult ; Aged ; Atherosclerosis ; blood ; complications ; Body Mass Index ; Brain Ischemia ; blood ; complications ; Carotid Intima-Media Thickness ; Case-Control Studies ; Cerebrovascular Disorders ; blood ; complications ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Inflammation ; Logistic Models ; Male ; Middle Aged ; Nicotinamide Phosphoribosyltransferase ; blood ; Risk Factors

Objective To investigate the optimal initial concentration of microRNA22 agomir in epilepsy model induced by lithium chloride-pilocarpine after single injection of lateral ventricle.Methods 36 rats with acute temporal lobe epilepsy were randomly divided into 6 groups:the control group and the other five groups were the experimental group.All epilepsy rats were selected for right lateral ventricle injection.The control group was given negative control reagent,while the experimental group were given 0.1 mmol/L,2.5 mmol/L,5 mmol/L,10 mmol/L,20 mmol/L different concentrations of miRNA22agomir reagent.6 rats in each group were randomly selected for acute phase experiment after 3 days of administration.The expression of P2X7 in hippocampus of epilepsy rats was determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).Results Compared with control group,the protein and mRNA expression of P2X7 reduced in all of the model group.The protein and mRNA expression level of P2X7 protein in hippocampus of rats injected with 2.5 mmol/L,5 mmol/L and 10 mmol/L in each experimental group were significantly lower than that in the other two groups (P ＜ 0.05).Moreover,the protein and mRNA expression level of P2X7 were the lowest at 2.5 mmol/L injection and 10 mmol/L,and there was no significant difference between the two groups (P ＞ 0.05).Conclusions The optimal onset concentration for unilateral lateral ventricle injection miRNA22 agomir treatment of temporal lobe epilepsy is 2.5 mmol/L.

Objective To investigate the effect of microRNA-22 (miRNA-22) on the expression of P2X7 receptor and inflammatory factors in hippocampus of rats with epilepsy. Methods Healthy SD male rats were intraperitoneal injected with lithium chloride and pilocarpine to induce epilepsy. Three days later, 45 epileptic rats were randomly divided into three groups: epilepsy group( EP group), miRNA-22 agomir group (EF+agomir group) and miRNA-22 agomir control group ( EF+agomir control group). Another 15 healthy rats were selected as control group(N group). The expression of P2X7 protein was detected by West- ern blot and the levels of miRNA-22, P2X7 mRNA, NF-κB mRNA ,IL-1β mRNA were detected by qRT-PCR. Nissl staining was used to observe the damage of Nissl bodies. Results Western blot result showed that compared with the N group(0. 91±0. 10), the level of P2X7 protein in EP group (1. 17±0. 052) in-creased, and the difference was statistically significant (t=-4. 11,P=0. 02). Compared with the EP+ag-omir control group(0. 94± 0. 14),the expression of P2X7 protein in EP+agomir group (0. 66± 0. 06) de-creased and the difference was significant (t=-3. 10,P=0. 04). And the qRT-PCR results showed that compared with N group, the levels of P2X7mRNA (9. 08±0. 94), NF-κB mRNA (20. 10±2. 15) and IL-1β mRNA (50. 64±5. 42) in EP group increased(t=-14. 96,P<0. 05; t=-15. 38,P<0. 05; t=-15. 87,P<0. 05). The expression of P2X7mRNA (1. 31 ± 0. 64), NF-κB mRNA ( 2. 28 ± 1. 10) and IL-1β mRNA (2. 12±1. 20) in EF+agomir group decreased compared with EP group((9. 08± 0. 94),( 20. 10± 2. 15), (50. 64±5. 42)) and EF+agomir control group((7. 03 ±1. 90),(18. 72±1. 76),(47. 39±6. 16)), and the differences were statistically significant(F=29. 77, P<0. 01;F=98. 99, P<0. 05;F=96. 29, P<0. 01). Nissl staining results showed that a large number of morphologically abnormal and disintegrated Nissl bodies could be observed in the hippocampal CA1 and CA3 regions of EP group,which showed a smaller size,irreg-ular morphology,chromatin pyknosis,boundary blur between nucleus and cytoplasm. Compared with the nor-mal group, the difference was significant (P<0. 05). While in miRNA-22 agomir group, the disintegration of Nissl bodies was improved and the number of Nissl bodies increased. Conclusion Intraventricular injec-tion of miRNA-22 agomir can down-regulate the expression of P2X7 receptor and related inflammatory factors in hippocampus of epileptic rats, thus inhibiting seizures.

Molecular imaging is a developing research field and it has become a research hotspot.It integrates molecular biochemistry, data processing, nanotechnology, image processing and other technologies and has high specificity, high sensitivity, and high image resolution.It can provide qualitative, positioning, and quantitative data for clinical diagnosis.Clinically, 30% of epileptic patients develop into intractable epilepsy, but magnetic resonance imaging(MRI) can not detect structural lesions.These patients need accurate positioning in order to improve the effectiveness of epilepsy surgery.Because the current preoperative positioning methods have certain limitations, some epileptic patients still have recurrent seizures after the operation.Therefore, researchers continue to explore targeted tracers with high specificity and strong sensitivity.Various nanotechnology and functional magnetic resonance imaging methods are used to study the accurate localization methods of epilepsy.This paper summarized and analyzed the latest research of molecular imaging technology in China and abroad, such as the latest research of single photon emission computed tomography(SPECT) and positron emission tomography(PET) molecular imaging, the application of various nanotechnology combined with functional magnetic resonance in the accurate diagnosis and treatment of epilepsy, and various targeted tracers that haven been developed at present.The results suggest that the continuous improvement of quantitative image analysis, the integration of multi-mode imaging, the development of PET radioactive tracers, and the combination of nanotechnology and functional magnetic resonance imaging(fMRI) will facilitate a more comprehensive understanding of the pathophysiological mechanism of epilepsy.It is promising to realize the accurate diagnosis and treatment of intractable epilepsy.

The brain is an important organ in the human body with high metabolic requirements, and epilepsy, as a common neurological disease, also exhibits high metabolic characteristics in its lesion area. At present, controlling seizures caused by drug-resistant epilepsy or specific metabolic defects through metabolic regulation has shown good anti epileptic effects. In recent years, people have become increasingly interested in the relationship between brain metabolism and epileptic seizures. So far, several new anti epileptic therapies targeting metabolic pathways have been proposed, including inhibition of glycolysis, targeted lactate dehydrogenase, and dietary therapy. It is highly promising to intervene in epilepsy by regulating brain metabolism, but currently we still lack a thorough understanding of the role of brain metabolism in controlling epilepsy. This review aims to gain a deeper understanding of energy metabolism in the brain and its correlation with epilepsy, emphasizing the regulation of neuronal excitability through glycolysis, in order to search for effective anti epileptic therapies, in order to better understand the role of glycolysis in epileptic seizures and reveal potential therapeutic targets for epilepsy.