Volume 7, Issue 1

Background: The purpose of this study was to identify predictors and preventative treatments for post-stroke epilepsy (PSE). Methodology: Eighty-four patients who had suffered a cerebrovascular insult (within 72 hours) were recruited and divided into two groups: an EP group (patients with seizures after stroke) and a NEP group (patients without seizures after stroke). The NEP group was then subdivided into three groups: a control group, a GABA (γ-aminobutiric acid) group (received GABA orally), and a CCB group (received calcium channel blocker nimodipine orally). Patient groups were compared by gender, age, past medical history, stroke type, number of lesions, and position and stroke severity (using Scandinavian stroke scale, SSS). Forearm venous blood was sampled, and high performance liquid chromatography (HPLC) was used to measure plasma levels of neurotransmitters and Ca 2+ . Patients then received 14 days of drug intervention. One month after drug withdrawal, GABA, glutamate (Glu) and Ca 2+ concentrations in plasma were measured again. Results: The number of previous strokes, size of infarction, presence of multiple lesions, localization to the cortex, and SSS were statistically significant between the two groups ( P < 0.05). In the EP group, the Glu concentration was greater and the Ca 2+ concentration was lower than in the NEP group ( P < 0.05). The results obtained after 1 month of therapy showed a reduction in Glu levels and an increase in GABA levels in the GABA group relative to the control NEP group ( P < 0.05), while the CCB group showed a decrease in the concentration of Glu and an increase in the concentrations of GABA and Ca 2+ relative to the NEP control group ( P < 0.05). Conclusions: We identified susceptibility factors for PSE and demonstrated that GABA and calcium antagonists may have a therapeutic use in the early prevention of PSE.

Background" Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that impairs a child’s ability to communicate with others. It also includes restricted repetitive behaviors, interests and activities. Symptoms manifest before the age of 3. In the previous studies, we found structural abnormalities of the temporal lobe cortex. High spine densities were most commonly found in ASD subjects with lower levels of cognitive functioning. In the present study, we retrospectively analyzed medical records in relation to the neonatal levels of total serum bilirubin (TSB), neuron-specific enolase (NSE), creatine kinase brain band isoenzyme (CK-BB), and neonatal behavior in ASD patients from Southern China. Methods: A total of 80 patients with ASD (ASD group) were screened for this retrospective study. Among them, 34 were low-functioning ASD (L-ASD group) and 46 were high-functioning ASD (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. For comparison with ASD cases, 80 normal neonates (control group) were selected from the same period. Biochemical parameters, including TSB, NSE and CK-BB in the neonatal period and medical records on neonatal behavior were collected. Results: The levels of serum TSB, NSE and CK-BB in the ASD group were significantly higher when compared with those from the control group (P < 0.01, or P < 0.05). The amounts of serum TSB, NSE and CK-BB in the L-ASD group were significantly higher when compared with those in the H-ASD group (P < 0.01, or P < 0.05). The Neonatal Behavioral Assessment Scale (NBAS) scores in the ASD group were significantly lower than that in the control group (P < 0.05). Likewise, the NBAS scores in the L-ASD group were significantly lower than that in the H-ASD group (P < 0.05). There was no association between serum TSB, NSE, CK-BB and NBAS scores (P > 0.05) in the ASD group. Conclusions: The neonatal levels of TSB, NSE and CK-BB in ASD from Southern China were significantly higher than those of healthy controls. These findings need to be investigated thoroughly by future studies with large sample.

The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compared to control, indomethacin reduced baseline CBF and cerebral delivery of oxygen (CDO 2 ) by about 26% (p < 0.01). Indomethacin reduced maximal BH time from 339 ± 51 to 319 ± 57 seconds (p = 0.04). In both conditions, the CDO 2 remained unchanged from baseline to the termination of apnea. At BH termination, arterial oxygen tension was higher following oral administration of indomethacin compared to control (4.05 ± 0.45 vs. 3.44 ± 0.32 kPa). The absolute increase in CBF from baseline to the termination of apnea was lower with indomethacin (p = 0.01). These findings indicate that the impact of CBF on maximal BH time is likely attributable to its influence on cerebral H + washout, and therefore central chemoreceptive drive to breathe, rather than to CDO 2 .

Mood disorders, including anxiety and depression, are thought to be characterized by disrupted neuronal synapses and altered brain plasticity. The etiology is complex, involving numerous regions of the brain, comprising a multitude of neurotransmitter and neuromodulator systems. Recently, new studies on the teneurins, an evolutionary ancient family of type II transmembrane proteins have been shown to interact with latrophilins (LPHN), a similarly phylogenetically old family of adhesion G protein-coupled receptors (GPCR) forming a transsynaptic adhesion and ligand-receptor pair. Each of the four teneurin proteins contains bioactive sequences termed the teneurin C-terminal associated peptides (TCAP-1–4), which possess a number of neuromodulatory effects. The primary structures of the TCAP are most closely similar to the corticotropin-releasing factor (CRF) family of peptides. CRF has been implicated in a number of diverse mood disorders. Via an association with dystroglycans, synthetic TCAP-1 administration to both embryonic and primary hippocampal cultures induces long-term changes in neuronal structure, specifically increased neurite outgrowth, dendritic branching, and axon growth. Rodent models treated with TCAP-1 show reduced anxiety responses in the elevated plus-maze, openfield test, and acoustic startle test and inhibited CRF-mediated cocaine-seeking behaviour. Thus the teneurin/TCAP-latrophilin interaction may play a major role in the origin, development and treatment of mood disorders.

The present review synthesizes lines of emerging evidence showing how several samples of children populations living in large cities around the world suffer to some degree neural, behavioral and cognitive changes associated with air pollution exposure. The breakdown of natural barriers warding against the entry of toxic particles, including the nasal, gut and lung epithelial barriers, as well as widespread breakdown of the blood-brain barrier facilitatethe passage of airborne pollutants into the body of young urban residents. Extensive neuroinflammation contributes to cell loss within the central nervous system, and likely is a crucial mechanism by which cognitive deficits may arise. Although subtle, neurocognitive effects of air pollution are substantial, apparent across all populations, and potentially clinically relevant as early evidence of evolving neurodegenerative changes. The diffuse nature of the neuroinflammation risk suggests an integrated neuroscientific approach incorporating current clinical, cognitive, neurophysiological, radiological and epidemiologic research. Neuropediatric air pollution research requires extensive multidisciplinary collaborations to accomplish the goal of protecting exposed children through multidimensional interventions having both broad impact and reach. While intervening by improving environmental quality at a global scale is imperative, we also need to devise efficient strategies on how the neurocognitive effects on local pediatric populations should be monitored.

Population stratification of functional gene polymorphisms is a potential confounding factor in genetic association studies. The Val66Met (rs6265) single-nucleotide polymorphism in the brain-derived neurotrophic factor gene ( BDNF ) exhibits one of the highest variabilities in terms of allelic distribution between populations. The present study reports the distribution of BDNF Val66Met alleles in a sample of healthy volunteers (N = 1124) selected from the Romanian population. Frequencies were 80.74% for the Val allele and 19.26% for the Met allele. The data from this study extends efforts to map the allelic distribution of BDNF Val66Met in populations around the world and emphasizes that population stratification should be controlled for in future studies that report phenotypic associations in samples from different populations.

Symptoms of cognitive dysfunction like memory loss, poor concentration, impaired learning and executive functions are characteristic features of both schizophrenia and Alzheimer’s disease (AD). The neurobiological mechanisms underlying cognition in healthy subjects and neuropsychiatric patients are not completely understood. Studies have focused on serotonin (5-hydroxytryptamine, 5-HT) as one of the possible cognitionrelated biomarkers. The aim of this review is to provide a summary of the current literature on the role of the serotonergic (5-HTergic) system in cognitive function, particularly in AD and schizophrenia. The role of the 5-HTergic system in cognition is modulated by the activity and function of 5-HT receptors (5-HTR) classified into seven groups, which differ in structure, action, and localization. Many 5-HTR are located in the regions linked to various cognitive processes. Preclinical studies using animal models of learning and memory, as well as clinical in vivo (neuroimaging) and in vitro ( post - mortem ) studies in humans have shown that alterations in 5-HTR activity influence cognitive performance. The current evidence implies that reduced 5-HT neurotransmission negatively influences cognitive functions and that normalization of 5-HT activity may have beneficial effects, suggesting that 5-HT and 5-HTR represent important pharmacological targets for cognition enhancement and restoration of impaired cognitive performance in neuropsychiatric disorders.

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

The present study used paired-picture paradigm, where either congruent or incongruent emotional expressions were presented side by side to measure the neural correlates underlying the processing of emotional conflict effect. Event-related potentials were recorded while participants identified whether the valences of the paired-picture were consistent or not. The results showed that incongruent and congruent picture pairs both elicited larger N2 (210-310 ms) amplitudes than neutral pairs. In contrast, the conflict picture pairs elicited a larger conflict slow potential (conflict SP, 700-1000 ms) than did the positive and neutral picture pairs. There was no significant difference in conflict SP amplitudes between incongruent and congruent picture pairs (i.e., the mean amplitudes of negative and positive picture pairs). The results demonstrated that emotional information was identified and processed during the stage from about 210 ms to 310 ms. However, the emotional conflict effect did not appear until late stage (700-1000 ms). These results supported the distributed attention theory of emotions (DATE).

Objectives Sleep problems represent a worldwide health concern but their prevalence and impacts are unknown in most non-European/North American countries. This study aimed to evaluate sleep-wake patterns, sleep quality and potential correlates of poor sleep in a sample of the urban Georgian population. Methods Analyses are based on 395 volunteers (267 females, 128 males, aged 20-60 years) of the Georgia Somnus Study. Subjects completed the Pittsburgh Sleep Quality Index (PSQI) and the Beck Depression Inventory-Short Form. Sociodemographic information and self-reported height and weight were collected. Results 43% of subjects had poor sleep quality (PSQI > 5). Further, 41% had low sleep efficiency, 27.6% slept 6 hours or less, 32.4% went to bed after midnight, 27.6% snored, 10.6% were taking sleep medication, and 26.8% had sleep maintenance problems as occurring three or more times a week. The latest bedtime, rise time, and gender effect on these variables were found in the age group 20-29 years. PSQI global score showed a significant age but not gender difference. The economic status and the depression score were two significant predictors of sleep quality. Conclusions Poor sleep quality has a high prevalence and is strongly linked to the economic status. Study findings call for a global assessment of sleep problems in countries where sleep disturbances represent an insufficiently recognized public health issue.

Presenilin 1 (PS1) and PS2 are evolutionarily conserved transmembrane proteins of the aspartyl protease family. Initially, they were reported to be associated with the early onset of familial, early-onset Alzheimer’s disease. PS1 has been implicated in several crucial brain functions including developmental processes, synaptic plasticity, and processing of various molecules, while PS2 has been poorly studied and is considered to be a compensatory partner of PS1. Certain controversial reports have suggested that PS2 has a role in apoptosis, though the underlying mechanism is not clear. To ascertain the role of PS2 in apoptosis, mouse neuroblastoma cells (Neuro2a) were transfected with a cDNA construct encoding full length mouse PS2 and analyzed for viability, expression of PS1, PS2, Bax and p53, Bax protein, and status of chromatin condensation. Our results showed reduced viability, condensed chromatin and higher expression of Bax at mRNA and protein levels, but no change in the expression of p53 and PS1 in PS2-overexpressing Neuro2a cells. Thus, it is evident that PS2, independent of PS1, is associated with apoptosis via a Bax-mediated pathway. These findings might help in the understanding of the involvement of PS2 in apoptosis and its associated brain disorders.

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system (CNS). Various genetic and environmental factors have been identified to contribute to etiology of MS and NMO. Aquaporin 4 (AQP4), is the most abundant water channel in CNS. AQP4 is expressed in astrocytes of the brain, spinal cord, optic nerve and supportive cells in sensory organs. In contrast to MS, immunoreactivity of AQP4 is abolished in NMO lesions. However, conflicting results have been reported regarding the association between AQP4 polymorphisms and demyelinating disorders. Considering the ethnic differences of genetic variations, replications in other cohorts are required. In this study, single nucleotide polymorphisms (SNPs) of AQP4 gene in patients with NMO/neuromyelitis optica spectrum disorders (NMOSD), and MS in the Northern Han Chinese population were examined. Six selected AQP4 SNPs were genotyped by high-resolution melting (HRM) method. Compared with healthy control (HC), there was no significant difference of AQP4 allele and genotype frequency in MS or NMO/NMOSD group. This study showed no significant association of common AQP4 SNPs with MS or NMO/NMOSD, strongly suggesting that polymorphisms of AQP4 gene are unlikely to confer MS or NMO/NMOSD susceptibility, at least in Northern Han Chinese population.

Objective Progressive cerebral infarctions increase mortality and functional disability through mechanisms which have yet to be completely understood. The goal of this study was to explore the dynamic changes of serum C-reactive protein (CRP), fibrinogen (FIB) and D-dimer (D-D) in order to better characterize progressive cerebral infarction. Methods The amount of serum CRP, FIB and D-D was measured in 82 patients with progressive cerebral infarction by taking samples from the internal carotid artery (progressive group), and in 186 patients with non-progressive cerebral infarction (non-progressive group) by using an automatic biochemical analyzer during the next day (day 1), day 3, day 7, and day 14 after being admitted to hospital. Carotid vascular ultrasound and neurological deficit score (National Institutes of Health Stroke Scale, NIHSS) were also recorded. Results Carotid stenosis ratio was significantly higher in the progressive group than in the non-progressive group (P < 0.01) on admission. In the progressive group, CRP increased significantly on day 3, followed by a decline on day 7 and day 14, but was significantly higher than those in the non-progressive group (P < 0.01). The levels of FIB and D-D increased in the progressive group more than those in the non-progressive group on day 3, day 7, and day 14 (P < 0.01). The progressive group patients’ NIHSS score gradually increased after admission, which was opposite to the non-progressive group patients whom followed a downward trend. The difference between these two groups was significant (P < 0.01). Conclusion Observing changes of CRP, FIB and D-D may contribute to early identification and timely treatment of progressing ischemic strokes.

The association between verbal fluency deficit in Alzheimer's disease (AD) and deterioration of specific white matter (WM) tracts is currently not well understood. Using diffusion tensor imaging, we investigated a possible association between the left uncinate fasciculus, which has been implicated in word retrieval, and verbal fluency deficit in AD. A comparison of five properties of WM (fractional anisotropy, mode of anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) in 28 mild AD patients and 26 age-, gender- and education-matched healthy controls revealed significant group differences in a range of WM tracts. Looking specifically at diffusion parameters’ values for the left uncinate fasciculus and verbal fluency scores in the AD group, we observed a positive trend between the letter fluency scores and mode of anisotropy values ( r = 0.36, p = 0.55). Thus, our data suggest more global WM damage in mild AD, which also includes damage to the left uncinate fasciculus. However, damage to this particular tract is not robustly associated with verbal fluency decline at this stage of disease.

Objective A possible relationship between fibrosis along the route of cerebrospinal fluid (CSF) flow and the subsequent development of hydrocephalus has been indicated in previous studies. These changes in the fibrosis index may reflect the severity of hydrocephalus and could potentially become a diagnostic tool. The object of this study was to analyze the levels of procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), hyaluronic acid (HA), and laminin (LN) in the CSF of patients with post-traumatic hydrocephalus and determine the significance of their presence. Subjects and methods Forty-four patients were included in the study: 24 patients with shunt-dependent post-traumatic hydrocephalus (group A - hydrocephalus group); ten brain trauma patients without any sign of hydrocephalus (group B - trauma group); ten patients without brain trauma and hydrocephalus (group C - normal control group). CSF levels of PICP, PIIINP, HA, LN and transforming growth factor-β1(TGF-β1) were detected using enzyme-linked immunosorbent assay (ELISA). Results Levels of PICP, PIIINP, HA, and LN in the group of hydrocephalus patients were significantly higher than those in the post-trauma patients without hydrocephalus (p < 0.05) and normal control patients (p < 0.05). Moreover, the increased levels of PICP, PIIINP, HA, and LN were positively correlated with the level of TGF-β1 (p < 0.05). Conclusion We demonstrated an increase of fibrosis factors including PICP, PIIINP, HA, and LN, that was positively correlated with TGF-β1 levels. This indicates an important role for the process of fibrosis in the development of post-traumatic chronic hydrocephalus and shows the potential utility of PICP, PIIINP, HA, and LN as a diagnostic index in shunt-dependent post-traumatic chronic hydrocephalus.

We all experience at least occasional lapses in attention but in some neurological conditions, loss of attention is pervasive and debilitating. Treating deficits in attention first requires an understanding of the neurobiology of attention, which we now understand to be a set of different cognitive processes. Cholinesterase inhibitors are already established as effective attentional enhancers used in the treatment of certain dementias. Other stimulant agents such as modafanil, amphetamine and methylphenidate have demonstrated limited success in healthy individuals where attention is already optimal and clinical trials in patients with neurological disease are sparse. Dietary and lifestyle changes are gaining increasing prominence, as are experimental treatments such as deep brain stimulation and transcranial magnetic stimulation. As the therapeutic arsenal widens, clinicians will be able to match specific treatments to selective deficits in attention, giving patients a tailored management plan. Here we review common diseases that impair attention and emphasise how an understanding of attentional processing within the brain might lead to improved therapeutic strategies.

Superficial temporal artery-middle cerebral artery (STA-MCA) bypass [1,2] is an important and effective type of surgical revascularization that is widely used in the treatment of ischemic cerebral artery disease. However, a means of predicting its postoperative efficacy has not been established [3,4]. The present study analyzes the correlation between preoperative perfusion parameters (obtained using dynamic susceptibility contrast-enhanced perfusion imaging, DSC-PI) and postoperative long-term prognosis (using modified Rankin Scale, mRS scores). The preoperative perfusion parameters were defined by a combination of perfusion-weighted imaging and the Alberta Stroke Program Early Computerized Tomography Score (PWI-ASPECTS) and included cerebral blood flow (CBF)-ASPECTS, cerebral blood volume (CBV)-ASPECTS, mean transit time (MTT)-ASPECTS, and time to peak (TTP)-ASPECTS. Preoperative and postoperative scores were determined for 33 patients that received a unilateral STA-MCA bypass in order to discover the most reliable imaging predictive index as well as to define the threshold value for a favorable clinical outcome. The results showed that all of the PWI-ASPECTS scores were significantly negatively correlated with clinical prognosis. Receiver operating curve (ROC) analysis of the preoperative parameters in relation to long term prognosis showed the area under curve (AUC) was maximal for the CBF-ASPECTS score (P = 0.002). A preoperative score of less than six indicated a poor postoperative prognosis (sensitivity = 74.1%, specificity = 100%, AUC = 0.843). In conclusion, preoperative PWI-ASPECTS scores have been found useful as predictive indexes for the long-term prognosis of STA-MCA bypass patients, with higher scores indicating better postoperative long-term outcomes. As the most valuable prognostic indicator, the preoperative CBF-ASPECTS score has potential for use as a major index in screening and outcome prediction of patients under consideration for STA-MCA bypass surgery.

Objectives Alzheimer’s disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD) are the most common causes of dementia; however, their overlapping clinical syndromes and involved brain regions make a differential diagnosis difficult. We aimed to identify the differences in the cognition and motor cortex excitability between AD and bvFTD patients. Methods Twenty-seven AD patients and 30 bvFTD patients were included in the study. Each participant received a neurological evaluation. Cognitive event-related potentials (P300) were recorded during an auditory oddball task. Next, the excitability of the motor cortex, including the resting, facilitated motor threshold (RMT and FMT) and cortical silent period (CSP), were assessed during transcranial magnetic stimulation (TMS). Results The bvFTD patients exhibited significantly longer P300 latencies compared with AD patients. There was a significant negative correlation between cognition and P300 latency in the bvFTD group. The AD patients showed significantly reduced RMT and FMT values compared to the bvFTD group; however, no significant correlation was found between AD severity and the excitability of the motor cortex. Conclusions Cognition and motor cortical functions are different between AD and bvFTD patients. Noninvasive electrophysiological examinations have the potential to identify unique pathophysiological features that can be used to differentially diagnose AD and bvFTD patients.

The purpose of the present study was to determine whether early bilingual Basque-Spanish speakers, who acquired Spanish by the age of 5, comprehend Spanish wh -dependences as effortlessly as native Spanish speakers. Given that Basque and Spanish are structurally different languages, we hypothesized that predictive processing strategies from the first language (L1) would interfere with predictive processing strategies in the second language (L2). More specifically, since Basque overtly marks the semantic role of agent/subject position, whereas Spanish overtly marks the role of patient/object position, we looked at whether the difference in overt marking of semantic roles would affect comprehension of subject vs . object quien “who” and qué “which” direct and embedded questions as well as subject vs . object relative clauses introduced by qué . The main finding of the study is that overall early Basque-Spanish bilinguals needed more time for the comprehension of wh -dependencies in Spanish compared to native Spanish speakers, as indicated by statistically significant group differences in response times in 9 out of 10 conditions. The results of this exploratory study indicate that a difference in overt marking of semantic roles between the two languages affects the ease of processing of Spanish wh -dependencies in early Basque-Spanish bilinguals, interfering with their ability to make native-like predictions in L2.

Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.

Schizophrenia is a complex polygenic disorder of unknown etiology. Over 3,000 candidate genes associated with schizophrenia have been reported, most of which being mentioned only once. Alterations in cognitive processing - working memory, metacognition and mentalization - represent a core feature of schizophrenia, which indicates the involvement of the prefrontal cortex in the pathophysiology of this disorder. Hence we compared the gene expression in postmortem tissue from the left and right dorsolateral prefrontal cortex (DLPFC, Brodmann's area 46), and the medial part of the orbitofrontal cortex (MOFC, Brodmann's area 11/12), in six patients with schizophrenia and six control brains. Although in the past decade several studies performed transcriptome profiling in schizophrenia, this is the first study to investigate both hemispheres, providing new knowledge about possible brain asymmetry at the level of gene expression and its relation to schizophrenia. We found that in the left hemisphere, twelve genes from the DLPFC and eight genes from the MOFC were differentially expressed in patients with schizophrenia compared to controls. In the right hemisphere there was only one gene differentially expressed in the MOFC. We reproduce the involvement of previously reported genes TARDBP and HNRNPC in the pathogenesis of schizophrenia, and report seven novel genes: SART1, KAT7, C1D, NPM1, EVI2A, XGY2 , and TTTY15 . As the differentially expressed genes only partially overlap with previous studies that analyzed other brain regions, our findings indicate the importance of considering prefrontal cortical regions, especially those in the left hemisphere, for obtaining disease-relevant insights.

As a part of Alzheimer’s disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein expression levels of mTOR and its downstream pathways as well as pro-inflammatory cytokines (PICs) in the brain of AD rats. We further examined the effects of blocking mTOR on PICs, namely IL-1β, IL-6 and TNF-α. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in the hippocampus of AD rats compared with controls. Blocking mTOR by using rapamycin selectively enhanced activities of IL-6 and TNF-α signaling pathways, which was accompanied with an increase of Caspase-3, indicating cellular apoptosis and worsened learning performance. In conclusion, our data for the first time revealed specific signaling pathways engaged in the development of AD, including a regulatory role by the activation of mTOR in PIC mechanisms. Stimulation of mTOR is likely to play a beneficial role in modulating neurological deficits in AD.Targeting one or more of these signaling molecules may present with new opportunities for treatment and clinical management of AD

Ulinastatin [urinary trypsin inhibitor (UTI)] plays an important role in the protection of organs against ischemic injury during severe inflammation. The purposes of this study were to examine the effects of UTI on the levels of pro-inflammatory cytokines (PICs) and protein expression of PIC receptors in the neocortex and hippocampus CA1 region of rats after transient global ischemia induced via cardiac arrest (CA). Specifcally, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were analyzed. CA was induced by asphyxia followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were employed to determine PICs and their receptors in the neocortex and hippocampus. Our results show that IL-1β, IL-6 and TNF-α were significantly elevated in the neocortex and hippocampal CA1 field after CA. This was accompanied with an increase in PIC receptors, namely IL-1R, IL-6R and TNFR1. Systemic injection of UTI attenuated the amplification of PIC signal pathways in these brain regions. UTI also improved the modified Neurological Severity Score and brain tissue edema in CA rats. Notably, UTI resulted in an increase in survival of CA rats as compared to CA rats without treatment. In conclusion, UTI plays a beneficial role in modulating transient global ischemia induced by CA by altering PIC signal mechanisms, but further studies are needed to draw more firm conclusions.

Intracerebral (IC) grafting of mesenchymal stem cells (MSCs) is not currently used in humans due to its potential complications. On the other hand, intra-arterial (IA) administration can be facilitated for engrafting of intensifed MSCs in the injured human brain. The study is designed to compare the two methods of MSC administration using IA and IC routes through the parameters of behavior, infarct volume, cell distribution, and MSC identification. An ischemic stroke model was generated in Sprague Dawley male rats. This experiment used MSCs/Ngn1 that express Neurogenin1 (Ngn1) to ensure grafted MSC maintenance. MSCs/Ngn1 or normal saline was administrated via the IC or IA route on day 3. All animals were randomly assigned into four groups (five rats in each group): IC-control, IA-control, IC-MSCs/Ngn1, or IA-MSCs/Ngn1. Motor behaviors, infarct volume, and distribution of superparamagnetic iron oxide (SPIO)-labeled cells on magnetic resonance imaging (MRI) were compared from each group. There were no baseline differencess in motor behaviors or infarct volume between IC-MSCs/Ngn1 and IA-MSCs/Ngn1. Hovever, the IA-MSCs/Ngn1 group showed the greatest recovery on Rotarod testing and adhesive removal tests (p = 0.003 and p = 0.009 vs. IC-MSCs/Ngn1, respectively). The IA-MSCs/Ngn1 group also had more evenly distributed SPIO-labeled cells on MRI. The results suggest that IA administration is likely to be benefcial for humans based on its ability to improve behavioral outcomes and ensure even MSC engrafting.