The pattern of allelic loss of heterozygosity (LOH) and PTEN mutations appear to be associated with the progression of gliomas leading to a decrement in the survival rate of patients. This present study was carried out to determine the LOH and PTEN mutational status in glioma patients and its association with patients' survival.
Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications.
Cerebral hypoperfusion involved a reduction in cerebral blood flow, leading to neuronal dysfunction, microglial activation and white matter degeneration. The effects on the blood-brain barrier (BBB) however, have not been well-documented. Here, two-vessel occlusion model was adopted to mimic the condition of cerebral hypoperfusion in Sprague-Dawley rats. The BBB permeability to high and low molecular weight exogenous tracers i.e. Evans blue dye and sodium fluorescein respectively, showed marked extravasation of the Evans blue dye in the frontal cortex, posterior cortex and thalamus-midbrain at day 1 following induction of cerebral hypoperfusion. Transmission electron microscopy revealed brain endothelial cell and astrocyte damages including increased pinocytotic vesicles and formation of membrane invaginations in the endothelial cells, and swelling of the astrocytes' end-feet. Investigation on brain microvessel protein expressions using two-dimensional (2D) gel electrophoresis coupled with LC-MS/MS showed that proteins involved in mitochondrial energy metabolism, transcription regulation, cytoskeleton maintenance and signaling pathways were differently expressed. The expression of aconitate hydratase, heterogeneous nuclear ribonucleoprotein, enoyl Co-A hydratase and beta-synuclein were downregulated, while the opposite observed for calreticulin and enhancer of rudimentary homolog. These findings provide insights into the BBB molecular responses to cerebral hypoperfusion, which may assist development of future therapeutic strategies.
Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.
Matched MeSH terms: Brain/metabolism; Brain/physiopathology*; Deep Brain Stimulation/methods*
Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.
The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen's d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers.
Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18°C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of the hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24 hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that, with longer survival time, the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans and may help explain the subtle cognitive changes experienced by patients after CPB.
Thirst and sodium appetite are the sensations responsible for the motivated behaviors of water and salt intake, respectively, and both are essential responses for the maintenance of hydromineral homeostasis in animals. These sensations and their related behaviors develop very early in the postnatal period in animals. Many studies have demonstrated several pre- and postnatal stimuli that are responsible for the developmental programing of thirst and sodium appetite and, consequently, the pattern of water and salt intake in adulthood in need-free or need-induced conditions. The literature systematically reports the involvement of dietary changes, hydromineral and cardiovascular challenges, renin-angiotensin system and steroid hormone disturbances, and lifestyle in these developmental factors. Therefore, this review will address how pre- and postnatal challenges can program lifelong thirst and sodium appetite in animals and humans, as well as which neuroendocrine substrates are involved. In addition, the possible epigenetic molecular mechanisms responsible for the developmental programing of drinking behavior, the clinical implications of hydromineral disturbances during pre- and postnatal periods, and the developmental origins of adult hydromineral behavior will be discussed.
We conducted a meta-analysis in order to investigate the relationships between PTEN gene mutations and the prognosis in glioma. The following electronic databases were searched for relevant articles without any language restrictions: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analyses were conducted using the STATA software (Version 12.0, Stata Corporation, College Station, Texas USA). Hazard ratio (HR) with its corresponding 95 % confidence interval (95%CI) was calculated. Six independent cohort studies with a total of 357 glioma patients met our inclusion criteria. Our meta-analysis results indicated that glioma patients with PTEN gene mutations exhibited a significantly shorter overall survival (OS) than those without PTEN gene mutations (HR = 3.66, 95%CI = 2.02 ~ 5.30, P < 0.001). Ethnicity-stratified subgroup analysis demonstrated that PTEN gene mutations were closely linked to poor prognosis in glioma among Americans (HR = 3.72, 95%CI = 1.72 ~ 5.73, P < 0.001), while similar correlations were not observed among populations in Sweden, Italy, and Malaysia (all P > 0.05). Our meta-analysis provides direct and strong evidences for the speculation of PTEN gene mutations' correlation with poor prognosis of glioma patients.
The universal probe is a tool devised to allow navigation-directed biopsies and drainage procedures to be performed in a simple manner using a single hardware and software.
The present study examines the gross anatomical features of anomalous lunate sulcus detected incidentally in a cadaveric brain and discusses its clinical importance. The absence of lunate sulcus was carefully studied in a dissected brain specimen. The absence of lunate sulcus was observed unilaterally on the right side of a cadaveric brain specimen. The lunate sulcus was clearly appreciated on the left side whilst on the right side it was absent. The right hemisphere of the cerebellum was also bigger in size as compared to the left. The absence of lunate sulcus is a rare finding, which may be detected incidentally. The anatomical knowledge of the lunate sulcus may be important for neurosurgeons operating on the occipital lobe and the radiologists interpreting CT scan.
Navigation in neurosurgery has expanded rapidly; however, suitable models to train end users to use the myriad software and hardware that come with these systems are lacking. Utilizing three-dimensional (3D) industrial rapid prototyping processes, we have been able to create models using actual computed tomography (CT) data from patients with pathology and use these models to simulate a variety of commonly performed neurosurgical procedures with navigation systems.
Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using compute unified device architecture, extending the previously proposed SurLens Visualization and computer aided hepatocellular carcinoma frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, USA. Significantly, our proposed framework is able to generate and extract points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the nodes and the edges. The framework is very efficient in providing greater interactivity as a way of representing the nodes and the edges intuitively, all achieved at a considerably interactive speed for instantaneous mapping of the datasets' features. Uniquely, the connectomic algorithm performed remarkably fast with normal hardware requirement specifications.
Brain injury such as traumatic brain injury (TBI) and stroke is the major cause of long-term disabilities in many countries. The increasing rate of brain damaged victims and the heterogeneity of impairments decrease rehabilitation effectiveness and competence resulting in higher cost of rehabilitation treatment. On the other hand, traditional rehabilitation exercises are boring, thus leading patients to neglect the prescribed exercises required for recovery. Therefore, we propose game-based approach to address these problems. This paper presents a rehabilitation gaming system (RGS) for cognitive rehabilitation. The RGS is developed based on a proposed conceptual framework which has also been presented in this paper.
This is the first investigation performed to detect the presence of the p53 mutation in Malay patients with gliomas. The p53 gene was amplified using polymerase chain reaction (PCR) from 33 fresh-frozen tumour tissues from patients histologically confirmed as glioma. Four hot spot areas that lie between exon 5 to 8 were screened for mutation by mean of non-isotopic "cold" single strand conformation polymorphism (SSCP) analysis and direct sequencing. The frequency of p53 gene mutation in gliomas examined was 33% (11 of 33). Five (45.5%) cases had mutation in exon 7, four (36.4%) had mutation in exon 8 and two (18.1%) had mutation in exon 6. Seven (63.6%) of 11 mutations were single nucleotide point mutations of which 5 were missense mutations, 1 was nonsense mutation and 1 was, silent mutation. Three (27.3%) showed insertion mutation and 1 (9.1%) showed deletion mutation. Of the point mutations, 57.1% were transitions and 42.9% were transversions. These results suggested that p53 mutations frequently occur in gliomas and this gene does play an important role in the tumourigenesis process of Malay patients with brain tumours.
Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.
The advancement of internet nowadays have drives the university students place great reliance on the internet for almost all matter. However, if the internet is heavily used, it may have a detrimental effect which could contribute to an Internet Addiction Disorders (IAD) among university students. IAD could create problem in developing relationships like normal people and appear to have low quality of memory. Thus, this is definitely not good to students. Knowing that by listening to Quran verse has a potential to improve the memory, hence this study is carried out. The study utilized a brain-computer interface Emotiv EPOC+, multichannel electroencephalography (EEG) detection during dual N-back tasks (spatial and verbal) where subjects were given with load level from 2-back to 3-back. Five (5) out of two hundred (200) participants of USIM’s students (20-23 years old) were recruited to continue with the brain scan experiment after getting a high score which indicated their severe level of addiction in a screening addiction test, Young’s Internet Addiction Test. Subjects were administered with a pre‐ and post‐tests to analyze and evaluate the effects of implementing Quran listening in their dailies for two months. The behavioral assessment exhibited accuracy increment between pre- and post- tests by 13.4% from 9.4%. While the EEG power value showed there were significant differences (p=0.002) in brainwaves between the pre- and the post- tests for 2 back; as the dominant brainwave found at the frontal and prefrontal cortex for delta and theta bands. The research revealed that the theta power band presented as the most dominant brain wave associated with N-back task for the enhancement of working memory which influence by the listening to Surah in Al-Quran.