An Immunological Approach to Increase the Brain’s Resilience to Insults

We have previously demonstrated the therapeutic potential of inducing a humoral response with autoantibodies to the N-methyl D-aspartate (NMDA) receptor using a genetic approach. In this study, we generated three recombinant proteins to different functional domains of the NMDA receptor, which is implicated in mediating brain tolerance, specifically NR1[21–375], NR1[313–619], NR1[654–800], and an intracellular scaffolding protein, Homer1a, with a similar anatomical expression pattern. All peptides showed similar antigenicity and antibody titers following systemic vaccination, and all animals thrived. Two months following vaccination, rats were administered the potent neurotoxin, kainic acid. NR1[21–375] animals showed an antiepileptic phenotype but no neuroprotection. Remarkably, despite ineffective antiepileptic activity, 6 of 7 seizing NR1[654–800] rats showed absolutely no injury with only minimal changes in the remaining animal, whereas the majority of persistently seizing rats in the other groups showed moderate to severe hippocampal injury. CREB, BDNF, and HSP70, proteins associated with preconditioning, were selectively upregulated in the hippocampus of NR1[654–800] animals, consistent with the observed neuroprotective phenotype. These results identify NR1 epitopes important in conferring anticonvulsive and neuroprotective effects and support the concept of an immunological strategy to induce a chronic state of tolerance in the brain.

Prenatal Exposure to Lamotrigine: Effects on Postnatal Development and Behaviour in Rat Offspring

Use of antiepileptic drugs (AEDs) in pregnancy warrants various side effects and also deleterious effects on fetal development. The present study was carried out to assess the effects of prenatal exposure to lamotrigine (LTG) on postnatal development and behavioural alterations of offspring. Adult male and female Sprague Dawley rats weighing 150–180 g b. wt. were allowed to copulate and pregnancy was confirmed by vaginal cytology. Pregnant rats were treated with LTG (11.5, 23, and 46 mg/kg, p.o) from gestational day 3 (GND 3) and this treatment continued till postnatal day 11 (PND 11). Offspring were separated from their dam on day 21 following parturition. LTG, at 46 mg/kg, p.o, produced severe clinical signs of toxicity leading to death of dam between GND 15 and 17. LTG, at 11.5 and 23 mg/kg, p.o, showed significant alterations in offspring’s incisors eruption and vaginal opening when compared to age matched controls. LTG (23 mg/kg, p.o) exposed female offspring expressed hyperactive behaviour and decreased GABA-A receptor expression when compared to control rats. These results reveal that prenatal exposure to LTG may impart differential postnatal behavioural alterations between male and female rats which paves way for further investigations.

Detection of Early Ischemic Changes in Noncontrast CT Head Improved with “Stroke Windows”

Introduction. Noncontrast head CT (NCCT) is the standard radiologic test for patients presenting with acute stroke. Early ischemic changes (EIC) are often overlooked on initial NCCT. We determine the sensitivity and specificity of improved EIC detection by a standardized method of image evaluation (Stroke Windows). Methods. We performed a retrospective chart review to identify patients with acute ischemic stroke who had NCCT at presentation. EIC was defined by the presence of hyperdense MCA/basilar artery sign; sulcal effacement; basal ganglia/subcortical hypodensity; and loss of cortical gray-white differentiation. NCCT was reviewed with standard window settings and with specialized Stroke Windows. Results. Fifty patients (42% females, 58% males) with a mean NIHSS of 13.4 were identified. EIC was detected in 9 patients with standard windows, while EIC was detected using Stroke Windows in 35 patients (18% versus 70%; P<0.0001). Hyperdense MCA sign was the most commonly reported EIC; it was better detected with Stroke Windows (14% and 36%; P<0.0198). Detection of the remaining EIC also improved with Stroke Windows (6% and 46%; P<0.0001). Conclusions. Detection of EIC has important implications in diagnosis and treatment of acute ischemic stroke. Utilization of Stroke Windows significantly improved detection of EIC.

Relationship between Neural Activity and Executive Function: An NIRS Study

Objective. This study examined the relationship between neural activity and executive function (EF) by near-infrared spectroscopy (NIRS). In addition, an oral reading span test (RST) was used to explore this association. Methods. Fifteen adults participated in the study. We used the RST and simple reading as the two tasks. Results. The RST score and cortical hemodynamic response in the left inferior frontal gyrus were significantly correlated. Conclusion. Based on the oral RST performance assessment and NIRS examination, the present findings suggest a relationship between EF and cortical activation.

Methods of EEG Signal Features Extraction Using Linear Analysis in Frequency and Time-Frequency Domains

Technically, a feature represents a distinguishing property, a recognizable measurement, and a functional component obtained from a section of a pattern. Extracted features are meant to minimize the loss of important information embedded in the signal. In addition, they also simplify the amount of resources needed to describe a huge set of data accurately. This is necessary to minimize the complexity of implementation, to reduce the cost of information processing, and to cancel the potential need to compress the information. More recently, a variety of methods have been widely used to extract the features from EEG signals, among these methods are time frequency distributions (TFD), fast fourier transform (FFT), eigenvector methods (EM), wavelet transform (WT), and auto regressive method (ARM), and so on. In general, the analysis of EEG signal has been the subject of several studies, because of its ability to yield an objective mode of recording brain stimulation which is widely used in brain-computer interface researches with application in medical diagnosis and rehabilitation engineering. The purposes of this paper, therefore, shall be discussing some conventional methods of EEG feature extraction methods, comparing their performances for specific task, and finally, recommending the most suitable method for feature extraction based on performance.

A Recurrent Increase of Synchronization in the EEG Continues from Waking throughout NREM and REM Sleep

Pointwise transinformation (PTI) provides a quantitative nonlinear approach to spatiotemporal synchronization patterns of the rhythms of coupled cortical oscillators. We applied PTI to the waking and sleep EEGs of 21 healthy sleepers; we calculated the mean levels and distances of synchronized episodes and estimated the dominant frequency shift from unsynchronized to synchronized EEG segments by spectral analysis. Recurrent EEG synchronization appeared and ceased abruptly in the anterior, central, and temporal derivations; in the posterior derivations it appeared more fluctuating. This temporal dynamics of synchronization remained stable throughout all states of vigilance, while the dominant frequencies of synchronized phases changed markedly. Mean synchronization had high frontal and occipital levels and low central and midtemporal levels. Thus, a fundamental coupling pattern with recurrent increases of synchronization in the EEG (“RISE”) seems to exist during the brain’s resting state. The generators of RISE could be coupled corticocortical neuronal assemblies which might be modulated by subcortical structures. RISE designates the recurrence of transiently synchronized cortical microstates that are independent of specific EEG waves, the spectral content of the EEG, and especially the current state of vigilance. Therefore, it might be suited for EEG analysis in clinical situations without stable vigilance.

Effect of Coadministration of Neurovite and Lamivudine on the Histomorphology of the Cerebellum of Wistar Rats

Introduction. Lamivudine is a nucleoside reverse transcriptase inhibitor antiretroviral agent used in the treatment of human immunodeficiency virus type 1 infection. This study was to investigate the effects of coadministration of neurovite and lamivudine on the histomorphology of the cerebellum of Wistar rats. Materials and Methods. Twenty Wistar rats were divided equally into four groups. Group A animals were the control treated with distilled water. Groups B, C, and D animals were treated, respectively, with therapeutic dose of lamivudine (4.28 mg/kg), a combination of lamivudine (4.28 mg/kg) and neurovite (7.05 mg/kg), and neurovite (7.05 mg/kg) alone, daily. The rats were sacrificed using chloroform inhalation, processed, and stained using H&E method. Results. There was severe cellular degeneration with dystrophic changes, vacuolization in the molecular and granular layers, and aggregation of swollen Purkinje cells in group B animals compared with group C animals which showed only slight cellular dystrophy and inflammation. The mean cellular population was significantly (P<0.05) higher in the treatment groups compared with the control. Conclusion. There was amelioration of damage of the cerebellum in the animals treated with neurovite and lamivudine combination compared to animals treated with only lamivudine. Therefore, there is need to give neurovite to patients on lamivudine therapy.

Caspase-3 and Survivin Expression in Primary Atypical and Malignant Meningiomas

Objective. Information about possible prognostic factors of the survival of patients with atypical and malignant meningiomas (AMM) is sparse. The aim of our study was to evaluate prognostic significance of apoptotic marker caspase-3 and apoptotic inhibitor survivin in a series of primary AMM. Methods. 86 AMM (76 atypical and 10 malignant) were analyzed. Caspase-3 and survivin expression was evaluated immunohistochemically. The correlation between caspase-3, survivin, and other possible factors of meningioma recurrence was evaluated. Uni- and multivariate recurrence-free survival (RFS) and overall survival (OS) analyses were performed. Results. The intensity of caspase-3 expression correlated with the tumor grade (P=0.004), the proliferation index (P=0.019), and the mitotic count (P=0.013). Survivin tended to be more expressed in female patients (P=0.072). Survivin expression was stronger in malignant compared to atypical meningiomas, however, the difference was not statistically important (P=0.491). Neither survivin nor caspase-3 expression significantly predicted OS or RFS in patients with AMM. Conclusions. Strong caspase-3 expression on AMM cells could reflect a cellular attempt at the homeostatic autoregulation of the tumor size. Survivin expression on AMM cells is similar to the survivin expression reported on benign meningiomas. Caspase-3 and survivin expression has no prognostic significance on the survival of patients with AMM.

What Guides Visual Overt Attention under Natural Conditions? Past and Future Research

In the last decade, overt attention under natural conditions became a prominent topic in neuroscientific and psychological research. In this context, one central question is “what guides the direction of gaze on complex visual scenes?” In the present review recent research on bottom-up influences on overt attention is presented first. Against this background, strengths and limitations of the bottom-up approach are discussed and future directions in this field are outlined. In addition to that, the current scope on top-down factors in visual attention is enlarged by discussing the impact of emotions and motivational tendencies on viewing behavior. Overall, this review highlights how behavioral and neurophysiological research on overt attention can benefit from a broader scope on influential factors in visual attention.

Traveled Distance Is a Sensitive and Accurate Marker of Motor Dysfunction in a Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) is a common central nervous system disease associated with progressive physical impairment. To study the mechanisms of the disease, we used experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE is induced by myelin oligodendrocyte glycoprotein35–55 peptide, and the severity of paralysis in the disease is generally measured using the EAE score. Here, we compared EAE scores and traveled distance using the open-field test for an assessment of EAE progression. EAE scores were obtained with a 6-step observational scoring system for paralysis, and the traveled distance was obtained by automatic trajectory analysis of natural exploratory behaviors detected by a computer. The traveled distance of the EAE mice started to decrease significantly at day 7 of the EAE process, when the EAE score still did not reflect a change. Moreover, in the relationship between the traveled distance and paralysis as measured by the EAE score after day 14, there was a high coefficient of determination between the distance and the score. The results suggest that traveled distance is a sensitive marker of motor dysfunction in the early phases of EAE progression and that it reflects the degree of motor dysfunction after the onset of paralysis in EAE.