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Objectives Cognition and speech disorders are the most common symptoms of dementia in neurodegenerative disease. Here, we present a detailed clinical evaluation of a case of logopenic variant of primary progressive aphasia (lv-PPA), an atypical form of Alzheimer disease (AD), including cognitive testing over time, brain imaging, electrophysiology, and tests of olfactory function. Case report We present the case of a 58-year-old man suffering from progressive language difficulties who was finally diagnosed with lv-PPA. Clinical data included neuropsychological examinations, electrophysiology tests, neuroimaging, biomarkers, olfactory tests, and olfactory functional magnetic resonance imaging (fMRI). Results and Discussion The patient suffered from language disorders, including stumbling speech and forgetting appropriate words and how to pronounce some words. This had started 2 years earlier, and he had begun to deteriorate in recent months. In addition to his speech disorder, scores on the Mini Mental State Examination and Montreal cognitive assessment indicated that his cognition was affected. Structural imaging revealed no obvious hippocampal atrophy (score of 1), and molecular imaging showed hypometabolism and amyloid deposits in the temporal parietal region. The patient also presented with olfactory impairment. Although his odour detection threshold was normal, his cognitive threshold for scent recognition was significantly increased. Olfactory fMRI showed that activation of the whole brain and primary olfactory cortex was rare. Conclusion This case provides evidence suggesting that lv-PPA is an atypical form of AD, with symptoms including speech disorders and impaired cognition. This patient with lv-PPA presented with olfactory impairment.

Background This study evaluates the effect of butin against brain edema in intracerebral hemorrhage (ICH). Methodology ICH was induced by injecting bacterial collagenase in the brain and all the animals were separated into four groups such as control group, ICH group treated with vehicle, Butin 25 and 50 mg/kg group receives butin (25 and 50 mg/kg, i.p.)60 min after the induction of ICH in all animals. One day after neurological score, hemorrhagic injury and expressions of protein responsible for apoptosis and inflammatory cytokines were assessed in the brain tissue of ICH rats. Result Neurological scoring significantly increased and hemorrhagic lesion volume decreased in butin treated group of rats compared to ICH group. However, treatment with butin significantly decreases the ratio of Bax/Bcl-2 and protein expression of Cleaved caspase-3 than ICH group in dose dependent manner. Level of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) in the brain tissues were significantly decreased in the butin treated group than ICH group. In addition butin attenuates the altered signaling pathway of NF-κB in the brain tissues of ICH rats. Conclusion Our study concludes that butin attenuates the altered behavior and neuronal condition in ICH rats by reducing apoptosis and inflammatory response.

This study evaluates the protective effect of corilagin against Parkinsonismin Japanese encephalitis virus (JEV) induced Parkinson’s disease. The JaGAr-01 strain of virus was used to induce JE. The virus was injected into the rats (13 days age) at the midpoint between the two ears. Adult rats, 12 week after the inoculation of virus, were used for the further study. Corilagin (20 mg/kg) and levodopa with dopa decarboxylase inhibitor (LEV, 10 mg/kg) were administered intraperitoneally for the duration of one week. Bradykinesia and the levels of dopamine in the brain were estimated at the end of protocol. There was a significant decrease inthe motor function in the corilagin, LEV and LEV + corilagin treated groupscompared to the negative control group. However treatment with corilagin, LEV and LEV + corilagin significantly increases the level of dopamine in the brain compared to the negative control group. This study concludes that corilagin ameliorates the Parkinsonismin JEV induced Parkinsonism. Moreover it shows a synergistic effect when treated with LEV. Data presented in the investigation supports that corilagin can be used clinically.

Background Bipolar disorder (BD) is a mood disorder associated with cardiovascular and metabolic diseases and premature aging. Growth differentiation factor 15 (GDF-15) has emerged as a biomarker for cardiovascular risk and aging. Our aim was to compare plasma levels of GDF-15 between BD patients and controls, and to evaluate whether they were associated with clinical parameters. Methods Forty-six patients with type I BD (23 in euthymia and 23 in mania) and 33 healthy controls were recruited for this study. Plasma levels of GDF-15 were measured by immunoassay. Results The levels of GDF-15 were significantly higher (p < 0.001) in patients with BD in comparison with controls. In patients, GDF-15 levels correlated with age (rho = 0.434; p = 0.003) and illness duration (rho = 0.502; p = 0.001). Conclusion Our findings corroborate the view that BD is an illness associated with accelerated aging.

Although there are a few studies of portions of the vestibular system such as the vestibulocerebellar tract and the neural connectivity of the vestibular nuclei (VN), no study of the ipsilateral vestibulothalamic tract (VTT) (originating from the VN and mainly connecting to the lateral thalami nuclei) has been reported. In the current study, using diffusion tensor tractography (DTT), we investigate the reconstruction method and characteristics of the ipsilateral VTT in normal subjects. Thirty-three subjects were recruited for this study. For the ipsilateral VTT, the seed region of interest (ROI) was placed on the VN, which was isolated on the FA map using adjacent structures as follows: the reticular formation (anterior boundary), posterior margin of medulla and pons (posterior boundary), medial lemniscus (medial boundary) and restiform body (lateral boundary). The target ROI was placed at the lateral thalamic nuclei using known anatomical locations. The DTT parameters of the ipsilateral VTT were measured. The ipsilateral VTTs that originated from the vestibular nuclei ascended postero-laterally to the upper pons and antero-medially to the upper midbrain via the medial longitudinal fasciculus, and terminated the lateral thalamic nuclei. No significant differences were observed in DTT parameters of the ipsilateral VTT between the right and left hemispheres (p > 0.05). Using DTT, we reconstructed the ipsilateral VTT and observed the anatomical characteristics of the ipsilateral VTT in normal subjects. We believe that the methodology and results in this study could be helpful to researchers and clinicians in this field.

Background The pathophysiology of early brain injury (EBI) after subarachnoid hemorrhage (SAH) is poorly understood. The present study evaluates the influence of zinc transporter 3 (ZnT3) knockout and the depletion of vesicular zinc on EBI. Methodology SAH was induced in ZnT3 KO mice by internal carotid artery perforation. The changes in behavior were recorded at 24 hours after SAH. Hematoxylin-eosin, Nissl and TUNEL staining were performed to evaluate neuronal apoptosis. Data from mice with a score of 8-12 in intracerebral bleeding (i.e. moderate SAH), were analyzed. Results The degree of SAH-induced neuronal injury was directly correlated to the amount of blood lost, which in turn was negatively reflected in their behavior. The Wild Type (WT)-SAH group behaved poorly when compared to the knockout (KO)-SAH mice and their poor neurological score was accompanied by an increase in the number of apoptotic neurons. Conversely, the improvement of behavior in the KO-SAH group was associated with a marked reduction in apoptotic neurons. Conclusions These results suggest that ZnT3 knockout may have played a vital role in the attenuation of neuronal injury after SAH and that ZnT3 may prove to be a potential therapeutic target for neuroprotection in EBI.

Background Present study evaluates the neuroprotective effect of β-elemene alone and in combination with hyperbaric oxygen (HO) in traumatic brain injury (TBI). Methodology TBI was induced by dropping a weight from a specific height. All the animals were separated in to five groups (n=20) like control group; TBI group; β-elemene treated group which receives β-elemene (100 mg/kg, i.p.) half an hour after the injury; HO group which receives hyperbaric oxygen therapy and β-elemene + HO group which receives β-elemene (100 mg/kg, i.p.) half an hour after the injury and hyperbaric oxygen therapy. Neurological function was assessed to evaluate the effect of β-elemene in TBI rats. Thereafter level of inflammatory cytokines and expression of protein of inflammatory pathway was assessed in the brain tissues of TBI rats. In addition TUNEL assay was also done for the determination apoptosis in neuronal cells. Result Data of the report reveals that β-elemene alone and in combination with hyperbaric oxygen (HO) significantly decreases the neurological score Compared to TBI group. Moreover level of inflammatory cytokines and expression of LTR4 and casepase 3 significantly decrease and increase in the expression of IkB in β-elemene alone and in combination with hyperbaric oxygen (HO) treated group compared to TBI group. Data of TUNEL assay also reveals that β-elemene treated group shows significant decrease in the TUNEL positive cells and apoptosis index compared to TBI group. Conclusion Thus present study concludes the neuroprotective effect of β-elemene against TBI and it shows synergistic effect on TBI when treated with HO.

Background This study evaluated the protective effects of epifriedelinol (EFD) in a rat model of traumatic brain injury (TBI). Methodology TBI was induced by dropping a weight from a specific height. The animals were separated into control, TBI, and EFD 100 and 200 mg/kg groups. The latter received 100 and 200 mg/kg EFD, respectively, for 2 days beginning 30 min after inducing TBI. The neurological examination score, permeability of the blood–brain barrier (BBB), water content of the brain, cytokine levels, and oxidative stress parameters were measured in the rats. The effects of EFD on glial fibrillary acidic protein (GFAP)-positive cells were evaluated using immunohistochemistry. Result The EFD treatment significantly decreased the neurological score, permeability of the BBB, and water content of brain compared with the TBI group. The levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and oxidative stress were significantly decreased in the EFD-treated groups. The number of GFAP-positive cells was also significantly reduced in the EFD-treated groups. Conclusion EFD attenuates the secondary injury in TBI rats by reducing the serum cytokine levels and oxidative stress.

Arginine is one of the most versatile semi-essential amino acids. Further to the primary role in protein biosynthesis, arginine is involved in the urea cycle, and it is a precursor of nitric oxide. Arginine deficiency is associated with neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s diseases (AD). In this study, we administer arginine intracerebroventricularly in a murine model of AD and evaluate cognitive functions in a set of behavioral tests. In addition, the effect of arginine on synaptic plasticity was tested electrophysiologically by assessment of the hippocampal long-term potentiation (LTP). The effect of arginine on β amyloidosis was tested immunohistochemically. A role of arginine in the prevention of cytotoxicity and apoptosis was evaluated in vitro on PC-12 cells. The results indicate that intracerebroventricular administration of arginine improves spatial memory acquisition in 3xTg-AD mice, however, without significantly reducing intraneuronal β amyloidosis. Arginine shows little or no impact on LTP and does not rescue LTP deterioration induced by Aβ. Nevertheless, arginine possesses neuroprotective and antiapoptotic properties.

Tauopathies are neurodegenerative diseases, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD), in which tau protein aggregates within neurons. An effective treatment is lacking and is urgently needed. We evaluated two structurally similar natural compounds, morin and resveratrol, for treating tauopathy in JNPL3 P301L mutant human tau overexpressing mice. Rotarod tests were performed to determine effects on motor function. After treatment from age 11 to 14 months, brains of 26 mice were collected to quantify aggregated hyperphosphorylated tau by Thioflavin T and immunohistochemistry (IHC) and to quantify total tau (HT7 antibody) and hyperphosphorylated tau (AT8 antibody) in homogenates and a fraction enriched for paired helical filaments. Resveratrol reduced the level of total hyperphosphorylated tau in IHC sections (p=0.036), and morin exhibited a tendency to do so (p=0.29), while the two drugs tended to increase the proportion of solubilizable tau that was hyperphosphorylated, as detected in blots. Neither resveratrol nor morin affected motor function. One explanation of these results is that the drugs might interrupt a late stage in tau aggregation, after small aggregates have formed but before further aggregation has occurred. Further animal studies would be informative to explore the possible efficacy of morin or resveratrol for treating tauopathies.

Age-related effects were studied in 14 younger (M = 34 years) and 14 (M = 47 years) older healthy participants. Event-related potential (ERP) recording was done using a 256-channel EEG system. Results indicated that ERP is affected by advanced age. There was a significant difference in P200 mean latency between the younger participants and older participants for the target (low-probability) stimuli, but no such significance was evident for the P200 mean latency during the presentation of the standard (high-probability) stimuli. As for the P200 mean peak amplitude, the results for the target (low-probability) stimuli did show a significant difference between the two age groups, while the results for the standard (high-probability) stimuli did not show any significant difference between the two age groups. The results of this study are explained in light of aging effects on attentional recruitment and frontal lobe intactness.

Spinal Cord Injury (SCI) causes interruption along the severed axonal tract(s) resulting in complete or partial loss of sensation and motor function. SCI can cause tetraplegia or paraplegia. Both these conditions can have lifelong excessive medical costs, as well as can reduce life expectancy. Preclinical research showed that Photobiomodulation therapy (PBMT), also known as Low-level laser (light) therapy (LLLT), possesses reparative and regenerative capabilities that have the potential to be used as a complimentary or supplementary SCI therapy. Despite the promising effects of PBMT, there are still no standardized irradiation parameters (i.e. different wavelengths, power, fluence, irradiance, beam type, beam diameters, and irradiation time) and there is also a lack of standardized experimental protocol(s), which makes it difficult to compare different studies. It is, nonetheless, essential to standardize such irradiation parameters in order to provide better PBMTs. The aim of this study, therefore, is to evaluate the delivery of light in a 3D voxelated SCI rat model for PBMT using different irradiation parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat beam; and beam diameters: 0.04-1.2 cm) using Monte Carlo simulation. This study also aids in providing standardization for preclinical research for PBMT, which will eventually translate into clinical standardization upon clinical research studies and results.

We conducted an event-related potential (ERP) study using a 256-channel dense sensor array electroencephalography (EEG) system to examine how, and if the P200 neurophysiological signal is sexually dimorphic. We had two groups of participants: females (n= 15, mean age = 40.6 years old) and males (n = 15, mean age = 39.0 years old). ERPs from all participants were recorded while the participants performed an oddball task. Results showed that males on average had a significantly larger P200 peak amplitude and a significantly shorter P200 latency period. These results indicate that the P200 ERP is affected by sex. Therefore, suggesting that sex differences exist on an electrophysiological level, which may aid in better understanding of sex-biased biological influences, behaviors, neuropsychiatric disorders, and general brain function.

Background The aim of this work was to present the creation of appropriate tools to evaluate the coping strategies in Oral-Health-related Quality of Life (OHrQOL) implemented by persons with schizophrenia (PWS), the Schizophrenia Coping Oral Health Profile (SCOOHP), and the results of a feasibility study. Methods A qualitative investigation was conducted between June 2016 and May 2017. The first step included 26 semi-structured individual interviews, 20 with PWS and 6 with health professionals (HPs), and 2 focus groups (PWS and HPs) to explore the experiences of the participants and how they felt about coping strategies in OHrQOL. The second step was a feasibility study involving a statistical analysis to test the acceptability and internal consistency (Cronbach’s α) of the SCOOHP. Results The analysis of these interviews allowed for us to obtain 277 items from 3545 verbatim transcriptions related to various dimensions of OHrQOL. We presented the items selected in coping concepts in this study. After selecting items in several stages, we drew up the SCOOHP scale with 23 items (15 items for positive coping and 8 items for negative coping). The feasibility study showed good acceptability, good understanding of the items and good consistency reliability (α = 0.59). Conclusions This is the first study that has enabled us to draw up a specific tool to assess coping strategies in OHrQOL of PWS. A multicentre study involving a larger sample of PWS is underway in order to perform the psychometric validation of the SCOOHP. Trial registration Clinical Trials Gov NCT02730832. Date registered: 21 March 2016.

Background Baicalein, a bioactive flavonoid was explored for its capability to attenuate sevoflurane induced neuronal apoptosis and to improve behavioural and cognitive impairments. Sevoflurane is a frequently used inhalation anesthetic in neonates and children. Neonatal sevoflurane exposure causes widespread neurodegeneration and cognitive impairments. Development of compounds that could effectively prevent/reduce the adverse effects is of tremendous medical value. Methods Isolated groups of neonatal rats were regulated with baicalein (25, 50 or 100 mg/kg b.wt) from postnatal day 3 (P3) to P21 and were exposed to sevoflurane (3%; 6 h) on P7. Results: Baicalein inhibited sevoflurane induced neuroapoptosis significantly as assessed by TUNEL assay. The raised levels of cleaved caspase-3, Bad and Bax were down-regulated by baicalein with enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, c-IAP-2 and survivin expression. Baicalein regulated JNK/ERK signalling and also activated the PI3K/Akt pathway effectively as evident from the increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β levels. Baicalein, also improved the behaviour of animals in open filed and olfactory tests. The freezing responses and the performance in Morris Water Maze tests were enhanced. Conclusion Baicalein reduced neurodegeneration and improved learning and memory retention of rats and as well modulated PI3/Akt/GSK-3β and JNK/ERK signalling pathways.

Background To analyze whether magnesium has a neuroprotective effect during episodes that indicate a critical brain perfusion after aneurysmal subarachnoid hemorrhage (SAH). Methods 107 patients with aSAH were randomized to continuously receive intravenous magnesium sulfate with target serum levels of 2.0 – 2.5 mmol/l (n = 54) or isotonic saline (n = 53). Neurological examination and transcranial Doppler sonography (TCD) were performed daily, Perfusion-CT (PCT) was acquired in 3-day intervals, angiography in case of suspected vasospasm. The primary endpoint was the development of secondary infarction following episodes of delayed ischemic neurological deficit (DIND), elevated mean flow velocity (MFV) in TCD or pathological findings in PCT. Results In the magnesium group, 9 episodes of DIND were registered, none was followed by secondary infarction. In the control group, 23 episodes of DIND were registered, 9 were followed by secondary infarction (p < 0.05). In the magnesium group, 114 TCD-measurements showed an elevated MFV(> 140 cm/s). 7 were followed by new infarction. In control patients, 135 measurements showed elevated MFV, 32 were followed by new infarction (p < 0.05). 10 of 117 abnormal PCT-findings were followed by new infarction, compared to 30 of 122 in the control-group (p < 0.05). Conclusion DIND, elevated MFV in TCD and abnormal PCT are findings which are associated with an increased risk to develop delayed secondary infarction. The results of this analysis suggest that magnesium-treatment may reduce the risk to develop infarction in a state of critical brain perfusion.

Aims The aim of this study is to evalute the effects of methylphenidate and atomoxetine treatments on electroencephalography (EEG) signals in volunteer children diagnosed with Attention Deficit and Hyperactivity Disorder(ADHD). Methods The study contained 40 children all of whom were between the ages of 7 and 17. The participants were classified into two groups as ADHD (n=20), which was in itself divided into two groups as ADHD-MPH (ADHD- Metylphenidate treatment) (n=10) and as ADHD-ATX (ADHD-Atomoxetin treatment) (n=10), and one control group (n=20). Following the first EEG recordings of the ADHD group, long-acting methylphenidate dose was applied to one ADHD group and atomoxetine dose was applied to the other ADHD group. The effect of optimal dosage is about for 4-6 weeks in general. Therefore, the response or lack of response to the treatment was evaluated three months after the beginning of the treatment. After methylphenidate and atomoxetine drug treatment, in order to obtain mean and maximum power values for delta, theta, alpha and beta band, the EEG data were analyzed. Results The EEG power spectrum densities in all the bands yielded similar findings in both methylphenidate and atomoxetine. Although statistically significant frequency values of the electrodes were amplitude and maximally varied, in general, they appeared mostly at both frontal and temporal regions for methylphenidate and atomoxetine. Conclusion Especially, after atomoxetine treatment, Quantitative Electroencephalography (QEEG) rates at frontal area electrodes were found statistically more significant than methylphenidate QEEG rates. What has been researched in this study is not only whether QEEG is likely to support the diagnosis, but whether changes on QEEG by treatment may be related to the severity of ADHD as well.

Background Present investigation evaluates the beneficial effect of fangchinoline on cerebral ischemia induced neuronal degeneration in neonatal rats and also postulates the possible mechanism of its action. Methodology Cerebral ischemia was produced by the ligation of right common carotid artery in neonatal rats on postnatal day 5 (P5) and further pups were treated with fangchinoline 3, 10 and 30 mg/kg, i.p. for the period of 3 days. Effect of fangchinoline was estimated by determining the brain injury and enzyme linked immunosorbent assay (ELISA) method was used for the estimation of pro-inflammatory mediators and markers of oxidative stress in the cerebral tissues of neonatal rats. Moreover western blot assay and histopathology study was also performed on the brain tissue. Results Result of this investigation reveals that the percentage of brain injury significantly reduces and enhancement of myelin basic protein in the cerebral tissues of fangchinoline than ischemic group. Treatment with fangchinoline attenuates the altered level of proinflammatory mediators and markers of oxidative stress in the cerebral tissue of cerebral ischemia induced neuronal injury neonatal rats. Moreover expressions of inducible nitric oxide synthtase (iNOS), vascular endothelial growth factor (VEGF), p53 and nuclear receptor factor-2 (Nrf2) in the brain tissue attenuated by fangchinoline treated group. Conclusion In conclusion, fangchinoline ameliorates the cerebral ischemia induced neuronal injury in neonatal rats by enhancing angiogenesis molecules.

Background The aim of this study was to present the different stages of development of the Schizophrenia Oral Health Profile (SOHP) questionnaire, aimed at assessing oral disorders and their impacts on functioning and psychosocial wellbeing for patients with schizophrenia (PWS) and to give the results of a feasibility study conducted in France Materials and methods The first step of this qualitative study was semi-structured interviews were conducted with 20 PWS and 6 health professionals (HP). A focus group integrating 4 PWS and 4 HP was also organised to identify the items of the SOHP. The data were analysed using a thematic analysis. Second, a feasibility study was conducted in a sample of 30 PWS who answered the SOHP questionnaire. The acceptability and understanding of the SOHP were evaluated, using a specific questionnaire. Results The semi-structured interviews and focus groups included 34 individuals in total. Items’ selection was done with several stages and led to a SOHP scale with 53 final items related to oral disorders and their impacts on functioning and psychosocial well-being. These items were classified in 13 preselected dimensions including one additional module related to the side effects of medications (11 items). The feasibility study showed good acceptability and understanding of the items of the SOHP scale. Conclusions The psychometric validation of the SOHP scale, involving a large sample of PWS, is currently in progress. The SOHP is important to evaluate PWS oral health needs and to offer appropriate strategies to improve oral health of this persons. Trial registration Clinical Trials Gov NCT02730832. Date registered: 21 March, 2016.

Background Primary open angle glaucoma (POAG) is the most common form of glaucoma, with a multifactorial etiology that results in retinal ganglion cell death and loss of vision. In this study, we assessed the effects of myricetin on the trabecular meshwork cells in POAG. Methods In the in-vivo model, glaucoma was induced in Sprague-Dawley rats by injecting hyaluronic acid into the anterior chamber of the eye (every week for six-weeks). Treatment group rats were administered myricetin (25, 50 or 100 mg/ kg body weight via oral gavage) each day for of six weeks. Results POAG TM cells exposed to myricetin (25, 50 or 100 μM) exhibited significantly lowered reactive oxidative species (ROS) levels and lipid peroxidation products. The expressions of transforming growth factors (TGFβ1/β2), vascular endothelial growth factor, and senescence markers (senescence associated-β-galactosidase, cyclin-dependent kinase inhibitors-p16 and p21) were substantially down-regulated in POAG TM cells exposed to myricetin. Myricetin effectively prevented IOP elevation in glaucoma-induced rats and decreased inflammatory cytokines (IL-1α, IL-1β, IL-6, Il-8, TNF-α) in the aqueous humor and POAG TM cells of glaucoma-induced rats. Conclusion The observations of the study illustrate the protective effects of myricetin in glaucomatous TM cells.

Background The index to ring finger length (2D:4D) ratio is a proxy biomarker for prenatal exposure of sex hormones. Sex hormones are associated with the pathogenesis of ischemic stroke. The purpose of the study was to demonstrate the association between 2D:4D and ischemic stroke. Methodology This study retrospectively reviewed the data of 100 patients with first ever ischemic stroke between September, 2016 and June, 2017. The lengths of index finger and ring finger of both hands were measured using electronic calipers and calculated for 2D:4D ratios. Receive operating characteristic (ROC) mode was used to detect predicting performance of 2D:4D ratios for ischemic stroke. Results 2D:4D ratios in ischemic stroke patients were higher than controls in both hands (P < 0.05), except right 2D:4D ratio in females. The ROC analyses showed that the area under the curve (AUC) were 0.635 (95%CI: 0.527-0.743) for left 2D:4D ratio, and 0.647 for right (95%CI: 0.539-0.755) (P < 0.05). The AUC of left and right 2D:4D ratio in male were 0.667 (95%CI: 0.514-0.820) and 0.670 (95%CI: 0.519-0.822) (P < 0.05). In female, no significance were found in ROC analysis. And there were no correlation between 2D:4D value and stroke severity (P > 0.05). Conclusions The current study indicated that the diagnostic value of 2D:4D ratio was limited in ischemic stroke. Further research is required to explore the role of it in screening ischemic stroke.

Parkinson’s disease, the second major neurodegenerative disease, has created a great impact on the elder people. Although the mechanisms underlying Parkinson’s disease are not fully understood, considerable evidence suggests that neuro-inflammation, oxidative stress, mitochondrial dysfunction, cell proliferation, differentiation and apoptosis are involved in the disease. p38MAPK, an important member of the mitogen-activated protein family, controls several important functions in the cell, suggesting a potential pathogenic role in PD. This review provides a brief description of the role and mechanism of p38MAPK in Parkinson’s disease.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic neurocutaneous disorder, with heterogeneous manifestations. We aimed to review the clinical presentation of TSC and its association with epilepsy among Saudi population. This was a retrospective chart review study of 88 patients diagnosed with TSC with or without epilepsy. In 38.6% of patients, symptoms began before 1 year of age. The most frequent initial manifestations of TSC were new onset of seizures (68.2%), skin manifestations (46.6%) and development delay (23.9%). During the evolution of the disease 65.9% had epilepsy, 17% facial angiofibromas, 13.6% Shagreen patch, 18.2% heart rhabdomyomas and 12.5% retinal hamartomas. The genetic study for TSC diagnosis was done for 44 patients, 42 (95,4%) of them were genetically confirmed, for whom 13 patients had TSC1 mutation (29.5%), 29 patients were carrying TSC2 gene mutation (65.9%), Genetic test for TSC 1 and TSC 2 were negative for 2 patients (4.5%) despite positive gene mutation in their relative with TSC. The most common manifestations were central nervous system (predominantly epilepsy) and dermatological manifestations. Most of the patients develop epilepsy with multiple seizure types. TSC 2 mutation is more common than TSC 1 mutation.

Growing evidence suggests that stroke alters the phenotype of the peripheral immune system; better characterization of this response could provide new insights into stroke pathophysiology. In this investigation, we employed a deconvolution approach to informatically infer the cellular composition of the circulating leukocyte pool at multiple timepoints following stroke onset based on whole blood mRNA expression. Microarray data generated from the peripheral blood of 23 cardiovascular disease controls and 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset were obtained from a public repository. Transcriptomic deconvolution was used to estimate the relative counts of nine leukocyte populations based on the expression of cell-specific transcripts, and cell counts were compared between groups across timepoints. Inferred counts of lymphoid cell populations including B-cells, CD4+ T-cells, CD8+ T-cells, γδ T-cells, and NK-cells were significantly lower in stroke samples relative to control samples. With respect to myeloid cell populations, inferred counts of neutrophils and monocytes were significantly higher in stroke samples compared to control samples, however inferred counts of eosinophils and dendritic cells were significantly lower. These collective differences were most dramatic in samples collected at 5 and 24 hours post-symptom onset. Findings were subsequently confirmed in a second dataset generated from an independent population of 24 controls and 39 ischemic stroke patients. Collectively, these results offer a comprehensive picture of the early stroke-induced changes to the complexion of the circulating leukocyte pool, and provide some of the first evidence that stroke triggers an acute decrease in eosinophil counts.

Introduction This study investigated the effect of combining hypoglossal-facial nerve “side”-to-side neurorrhaphy and electrical myostimulation in a rat model of facial palsy. Methods Rats with facial nerve crush injury were subjected to control condition, monotherapy of either neurorrhaphy or electrical myostimulation, or bitherapy of the two treatments. After 1, 3, and 6 months, rats were performed the facial symmetry evaluation, electrophysiological examination and the retrograde labeling of motor neurons. Results As early as 3 months after injury, face symmetry significantly improved in rats of the bitherapy group. At 3 or 6 months after injury, either the parameters of electrophysiological examination or the number of labeled motor neurons were significantly increased in the bitherapy group than in any other group. Discussion The combination of neurorrhaphy and electrical myostimulation effectively promoted the functional recovery after facial nerve crush injury.

Present investigation aims to explore the protective effect of stachydrine against traumatic brain injury (TBI) and also investigate the molecular mechanism of its action. TBI was induced by the fall a hammer (450 g) from the height of 1.5 m. and later stachydrine was administered for 2 weeks starting 2 hr after the induction of TBI. Effect of stachydrine was determined by estimating modified neurological severity score (mNSS), percentage of water content in the brain and cognitive dysfunction in TBI rats. Moreover western blot assay, histopathology and enzyme linked immunosorbent assay (ELISA) tests were used to determine the effect of stachydrine on TBI injured rats. Result of the report suggests that stachydrine reduces the mNSS and percentage of water content in the brain and also attenuates the cognitive dysfunction in TBI injured rats. However data of western blot assay reports that stachydrine reduces the expression of PI3K/m-TOR/Akt pathway in the brain tissues of TBI rats. Concentration of interleukin (IL-1β), tumor necrosis factor-α (TNF-α) and interferon gamma (INF-γ) was reduces in stachydrine treated group than TBI group. Moreover expression of Nuclear factor-κB/Toll-like receptor 4 (NF-κB/TLR-4) protein was also decreased in stachydrine treated group than TBI group. Histopathology study on brain tissue reveals that the percentage of apoptotic cells was also reduced in stachydrine treated group than TBI group. Data of this investigation concludes that stachydrine protects the neuronal injury by attenuating the phosphatidylinositide 3-kinases/mammalian target of rapamycin/Protein kinase B (PI3K/m-TOR/Akt) and NF-κB/TLR-4 pathway in TBI injured rats.

Background Present investigation evaluates the neuroprotective effect of Bletilla striata on isoflurane induced neuronal injury rat model. Methodology Neuronal injury was induced by exposing the pups (P7) isoflurane (0.75%) in oxygen (30%) for the period of 6 hr and rats were treated with Bletilla striata at a dose of 35, 70 and 140 mg/kg, p.o. for the period of 21 days . At the end of protocol neurological score was estimated and serum concentration of inflammatory cytokines was estimated. Isolated brains tissue was prepared to perform immunohistochemical analysis, TUNEL assay and western blot assay. Results Result of the study reveals that treatment with BS significantly (p<0.01) reduces the neurological score compared to negative control group. Level of inflammatory cytokines in the serum and the expression of p-Akt, Bcl-xL and Bad protein were significantly attenuated in BS treated group. Moreover the cleaved caspase-3 and TUNEL positive cell was significantly (p<0.01) reduced in BS treated group compared to negative control group of rats. Conclusion Present study concludes that ethanolic extract of Bletilla striata protects the neuronal injury by reducing apoptosis in isoflurane induced neuronal injury rats.

Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer’s disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

The WWOX gene has a WW domain containing oxidoreductase, which is located at the common fragile site FRA16D at chromosome 16q23. WWOX is a tumor suppressor gene that has been associated with several types of cancer such as hepatic, breast, lung, prostate, gastric, and ovarian. Recently WWOX has been implicated in epilepsy, where studies show homozygous loss-of-function mutation lead to early-infantile epileptic encephalopathy, spinocerebellar ataxia, intractable seizures and developmental delay, and early lethal microcephaly syndrome with epilepsy. Here we investigate two consanguineous Saudi families and we identified three probands with epileptic encephalopathy. Whole exome sequencing revealed a novel homozygous mutation in the WWOX gene in one proband. In addition, we identified a previously reported WWOX mutation in two probands. Later on these findings were confirmed with Sanger sequencing. The underlying mechanism on how WWOX mutations lead to seizure remains elusive. To date very few WWOX mutations have been associated with neurological disorder and our newly identified mutations support the notion that WWOX play an important role in neurons and will aid in better diagnosis and genetic counseling.

Background The effects of nobiletin, a plant-derived flavonoid was examined against pentylenetetrazole (PTZ)-induced seizures. The study also aimed to assess whether nobiletin potentiated the effects of antiepileptic drug clonazepam (CZP). Methods PTZ (92 mg/kg, subcutaneous) was used to induce seizures in mice. Treatment groups (n = 18/group) received nobiletin (12.5, 25, or 50 mg/kg) via oral gavage for 6 consecutive days and 45 min prior to PTZ injection. CZP (0.015-2.0 mg/kg) was administered 15 min prior to PTZ. Skeletal muscle strength was assessed by measuring grip strength and Chimney test was performed to study the motor performance in animals. TUNEL assay was done to study neuro-apoptosis. RT-PCR and Western blot analysis were performed for assessment of mRNA and protein expressions. Results Nobiletin and CZP improved muscle strength and motor coordination and reduced seizure severity significantly. The administration of nobiletin and CZP, individually or in combination, downregulated seizure-induced increases in apoptotic cell count and apoptotic protein expression, modulated the expression of gamma-aminobutyric acid (GABA)A and glutamate decarboxylase 65 and restored the glutamate/GABA balance. Nobiletin and CZP administration significantly upregulated phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling. Conclusion Nobiletin exerted protective effect against seizures by regulating signaling pathways associated with epileptogenesis and potentiated the effects of CZP.