Light and the Brain: A Clinical Case Depicting the Effects of Light on Brainwaves and Possible Presence of Plasma-like Brain Energy.

Light is an electromagnetic radiation that has visible and invisible wavelength spectrums. Visible light can only be detected by the eyes through the optic pathways. With the presence of the scalp, cranium, and meninges, the brain is seen as being protected from direct exposure to light. For that reason, the brain can be viewed as a black body lying inside a black box. In physics, a black body tends to be in thermal equilibrium with its environment and can tightly regulate its temperature via thermodynamic principles. Therefore, a healthy brain inside a black box should not be exposed to light. On the contrary, photobiomodulation, a form of light therapy for the brain, has been shown to have beneficial effects on some neurological conditions. The proposed underlying mechanisms are multiple. Herein, we present our intraoperative findings of rapid electrocorticographic brainwave changes when the brain was shone directly with different wavelengths of light during awake brain surgery. Our findings provide literature evidence for light's ability to influence human brain energy and function. Our proposed mechanism for these rapid changes is the presence of plasma-like energy inside the brain, which causes fast brain activities that are akin to lightning strikes.

Functional Alteration in the Brain Due to Tumour Invasion in Paediatric Patients: A Systematic Review.

Working memory, language and speech abilities, motor skills, and visual abilities are often impaired in children with brain tumours. This is because tumours can invade the brain's functional areas and cause alterations to the neuronal networks. However, it is unclear what the mechanism of tumour invasion is and how various treatments can cause cognitive impairment. Therefore, this study aims to systematically evaluate the effects of tumour invasion on the cognitive, language, motor, and visual abilities of paediatric patients, as well as discuss the alterations and modifications in neuronal networks and anatomy. The electronic database, PubMed, was used to find relevant studies. The studies were systematically reviewed based on the type and location of brain tumours, cognitive assessment, and pre- and post-operative deficits experienced by patients. Sixteen studies were selected based on the inclusion and exclusion criteria following the guidelines from PRISMA. Most studies agree that tumour invasion in the brain causes cognitive dysfunction and alteration in patients. The effects of a tumour on cognition, language, motor, and visual abilities depend on the type of tumour and its location in the brain. The alteration to the neuronal networks is also dependent on the type and location of the tumour. However, the default mode network (DMN) is the most affected network, regardless of the tumour type and location.Furthermore, our findings suggest that different treatment types can also contribute to patients' cognitive function to improve or deteriorate. Deficits that persisted or were acquired after surgery could result from surgical manipulation or the progression of the tumour's growth. Meanwhile, recovery from the deficits indicated that the brain has the ability to recover and reorganise itself.

Characterisation of Primary Human Hippocampal Astrocyte Cell Culture Following Exposure to Hypoxia.

Background: The present study aimed to understand the characterisation of human hippocampal astrocyte following hypoxia exposure. Based on the preliminary screening, 15 min was chosen as the time point and the cells were exposed to different oxygen percentages. Methods: The Trypan blue viability assay used to examine cell death. Immunofluorescence assay, glial fibrillary acidic protein (GFAP) was used to portray the morphology of astrocytes. The hypoxia-inducible factor 1 (HIF-1) staining was performed to confirm hypoxia induced cell death and there was a dramatic expression of HIF-1α displayed in exposed astrocyte cells compared to the control. In molecular level, genes were chosen, such as glyceraldehyde 3-phosphate dehydrogenase (GAPDH), GFAP, HIF-1α and B-cell lymphoma 2 (Bcl-2) and ran the reverse transcription-polymerase chain reaction (RT-PCR). Results: Microscope revealed a filamentous and clear nucleus appearance in a control whereas the rupture nuclei with no rigid structure of the cell were found in the 3% oxygen. The control and hypoxia cells were also stained with the annexin V-fluorescein isothiocyanate (annexin V-FITC). Fluorescence microscope reveals astrocyte cells after hypoxia showed higher expression of nuclei but not in control. Merging PI and FITC showed the differences of nuclei expression between the control and hypoxia. In the molecular analysis, there were significant changes of GFAP, HIF-1α and Bcl-2 in hypoxia exposed cells when compared to the control group. Conclusion: Cells that were exposed to hypoxia (3% oxygen for 15 min) clearly showed damage. General view of human hippocampal astrocyte genomic response to hypoxia was obtained.

Introduction of a newly created AW stereotactic frame: a phantom-based accuracy evaluation and an initial experience in clinical usage.

BACKGROUND: A new stereotactic frame was created in 2015, based on a linear algorithm. It is called Albert Wong (AW) frame. A simple AW stereo-calculator was also designed based on Excel® (Microscoft Corporation, Redmond, WA) programme for the frame. OBJECTIVE: The aim of this study is to test the accuracy of the AW frame by a direct head to head comparison with CRW® frame (Integra Life Sciences, Plainsboro, NJ) on a phantom. METHODS: This is a prospective pilot cross-sectional phantom study with a total of 42 (21 for AW and 21 for CRW®) laboratory testings performed in 2017 at our institute to compare the accuracies of both frames in a consecutive manner. A phantom (BL phantom) was newly created, where targets can be placed at different heights and positions on a platform attached under the frame for accuracy testing comparing between the AW and CRW® frames. RESULTS: A comparable accuracy testing results were observed between the AW and CRW® frames of 0.64 mm versus 1.07 mm respectively. Approval from the local ethics committee for a clinical trial was obtained. We report on three case illustrations who had the AW frame-based biopsies with definitive diagnoses and without any post-biopsy related complication. CONCLUSION: AW frame successfully demonstrated a good accuracy of 0.64 mm in phantom testing using the BL phantom by a linear algorithmic calculation. The clinical trial with three patients demonstrated definitive diagnoses and safety with its use.

Transplantation of IGF-1-induced BMSC-derived NPCs promotes tissue repair and motor recovery in a rat spinal cord injury model.

Bone marrow-derived mesenchymal stem cells (BMSCs) have therapeutic potential for spinal cord injury (SCI). We have shown that insulin-like growth factor 1 (IGF-1) enhances the cellular proliferation and survivability of BMSCs-derived neural progenitor cells (NPCs) by downregulating miR-22-3p. However, the functional application of BMSCs-derived NPCs has not been investigated fully. In this study, we demonstrate that knockdown of endogenous miR-22-3p in BMSCs-derived NPCs upregulates Akt1 expression, leading to enhanced cellular proliferation. RNASeq analysis reveals 3,513 differentially expressed genes in NPCs. The upregulated genes in NPCs enrich the gene ontology term associated with nervous system development. Terminally differentiated NPCs generate cells with neuronal-like morphology and phenotypes. Transplantation of NPCs in the SCI rat model results in better recovery in locomotor and sensory functions 4 weeks after transplantation. Altogether, the result of this study demonstrate that NPCs derived with IGF-1 supplementation could be differentiated into functional neural lineage cells and are optimal for stem cell therapy in SCI.

Preliminary Comparison of Transseptal Microscopic Versus Endoscopic Transsphenoidal Surgery in a University Teaching Hospital.

Background: Transsphenoidal surgery (TSS) is an increasing preferred treatment for sella lesions. In a university teaching hospital, the novel endoscopic TSS was adopted with ongoing resident teaching. We evaluated a single institutional series of preliminary comparisons of transseptal microscopic with endoscopic TSS. Methods: A retrospective data analysis included 37 patients and 19 patients who underwent microscopic and endoscopic TSS, respectively. The demographic characteristics of the patients, intra-operative analyses, morbidity, mortality and visual assessments were included in this analysis. Results: The study included 31 men and 25 women, and median age at surgery was 49 years old (range 14-70 years old). There were no differences between the rates of cerebrospinal fluid (CSF) fistula, sinus complications, anterior pituitary hormone deficiency and diabetes insipidus between the groups. Total length of stay and intensive care unit stay were similar between the groups. Patients who underwent endoscopic TSS were at significantly increased risk of epistaxis (P = 0.010), respiratory event (P = 0.014) and post-operative visual deterioration prior to discharge (P = 0.032). Conclusion: Endoscopic TSS is a promising procedure that allows sufficient visualisation of the surgical field and adequate tumour removal. It is comparable to microscopic TSS but has a higher complication rate notably due to steep learning curve required to gain the expertise.

Vacuum Drains versus Passive Drains versus No Drains in Decompressive Craniectomies-A Randomized Controlled Trial on Subgaleal Drain Complication Rates (VADER Trial).

OBJECTIVE: Subgaleal drains are generally deemed necessary for cranial surgeries including decompressive craniectomies (DCs) to avoid excessive postoperative subgaleal hematoma (SGH) formation. Many surgeries have moved away from routine prophylactic drainage but the role of subgaleal drainage in cranial surgeries has not been addressed. METHODS: This was a randomized controlled trial at 2 centers. A total of 78 patients requiring DC were randomized in a 1:1:1 ratio into 3 groups: vacuum drains (VD), passive drains (PD), and no drains (ND). Complications studied were need for surgical revision, SGH amount, new remote hematomas, postcraniectomy hydrocephalus (PCH), functional outcomes, and mortality. RESULTS: Only 1 VD patient required surgical revision to evacuate SGH. There was no difference in SGH thickness and volume among the 3 drain types (P = 0.171 and P = 0.320, respectively). Rate of new remote hematoma and PCH was not significantly different (P = 0.647 and P = 0.083, respectively), but the ND group did not have any patient with PCH. In the subgroup analysis of 49 patients with traumatic brain injury, the SGH amount of the PD and ND group was significantly higher than that of the VD group. However, these higher amounts did not translate as a significant risk factor for poor functional outcome or mortality. VD may have better functional outcome and mortality. CONCLUSIONS: In terms of complication rates, VD, PD, and ND may be used safely in DC. A higher amount of SGH was not associated with poorer outcomes. Further studies are needed to clarify the advantage of VD regarding functional outcome and mortality, and if ND reduces PCH rates.

Quantum and Electromagnetic Fields in Our Universe and Brain: A New Perspective to Comprehend Brain Function.

The concept of wholeness or oneness refers to not only humans, but also all of creation. Similarly, consciousness may not wholly exist inside the human brain. One consciousness could permeate the whole universe as limitless energy; thus, human consciousness can be regarded as limited or partial in character. According to the limited consciousness concept, humans perceive projected waves or wave-vortices as a waveless item. Therefore, human limited consciousness collapses the wave function or energy of particles; accordingly, we are only able to perceive them as particles. With this "limited concept", the wave-vortex or wave movement comes into review, which also seems to have a limited concept, i.e., the limited projected wave concept. Notably, this wave-vortex seems to embrace photonic light, as well as electricity and anything in between them, which gives a sense of dimension to our brain. These elements of limited projected wave-vortex and limitless energy (consciousness) may coexist inside our brain as electric (directional pilot wave) and quantum (diffused oneness of waves) brainwaves, respectively, with both of them giving rise to one brain field. Abnormality in either the electrical or the quantum field or their fusion may lead to abnormal brain function.

Disconnecting surgery at alveus and cornu ammonis of hippocampus, amygdala superficialis, and amygdala medial nuclei for epilepsy associated with attention deficit hyperactivity disorder.

The neural basis for epilepsy and attention deficit hyperactivity disorder (ADHD) is currently incompletely known. We reported a young girl with both epilepsy and ADHD, who had a calcified lesion in the right basolateral amygdalo-hippocampal region extending to the ventral striatum. The child underwent disconnecting surgery and biopsy of the lesion. Fascinatingly, the child's behavior changed immediately after the surgery from inattentive and impulsive to nearly normal behavior experiencing no more breakthrough seizures since after 3 years of surgery. The Schaltenbrand Wahren Brain Atlas revealed alveus, cornu ammonis, amygdala superficialis, and medium as the disconnected region in this surgery.

Clinical Outcome of Tuberculous Meningitis with Hydrocephalus - A Retrospective Study.

BACKGROUND: To study the clinical outcome of tuberculous meningitis with hydrocephalus (TBMH) and the factors contributing to its poor clinical outcome. METHODS: Clinical data of 143 adult patients diagnosed with TBM over a 6-year period in two tertiary hospitals in Malaysia were retrospectively reviewed. Relevant clinical and radiological data were studied. Patients with TBMH were further analysed based on their clinical grade and rendered treatment to identify associated factors and outcome of this subgroup of patients. The functional outcome of patients was assessed at 12 months from treatment. RESULTS: The mean age of patients was 35.6 (12.4) years old, with a male gender predominance of 67.1%. Forty-four percent had TBMH, of which 42.9% had surgical intervention. In the good modified Vellore grade, 76.5% was managed medically with concurrent anti-tuberculosis treatment (ATT), steroids and osmotic agents. Four patients had surgery early in the disease as they did not respond to medical therapy and reported a good outcome subsequently. Poor outcome (65.2%) was seen in the poor modified Vellore grade despite medical and surgical intervention. Multivariate model multiple Cox regression showed significant results for seizure (adjusted hazard ratio [aHR]: 15.05; 95% CI: 3.73, 60.78), Glasgow coma scale (GCS) (aHR: 0.79; 95% CI: 0.70, 0.89) and cerebrospinal fluid (CSF) cell count (aHR: 1.11; 95% CI: 1.05, 1.17). CONCLUSION: Hydrocephalus was seen in 44% of patients in this study. GCS score, seizure and high CSF cell count were factors associated with a poor prognosis in TBM. Patients with TBMH treated medically (TBMHM) had better survival function compared to TBMH patients undergoing surgical intervention (TBMHS) (P-value < 0.001). This retrospective study emphasises that TBMH is still a serious illness as 47.6% of the patients had poor outcome despite adequate treatment.

Role of toll-like receptor 4 antagonist Lipopolysaccharide-Rhodobacter sphaeroides on acute stress-induced voluntary ethanol preference and drinking behaviour: In vivo Swiss Albino mouse model.

The present study focused on investigating the effect of toll-like receptor 4 (TLR4) antagonist Lipopolysaccharide-Rhodobacter sphaeroides(LPS-RS) on acute, stress-induced voluntary ethanol preference and drinking behaviour, neuronal components activation, and gene expression associated with stress and addictive behaviour. This study involved the exposure of restraint stress and social isolation using Swiss Albino mice. Two-bottle choice ethanol preference analysis was used in the evaluation of voluntary ethanol seeking and drinking behaviour. Several behavioural assessments were carried out to assess fear and anxiety-like behaviour, neuromuscular ability, motor coordination and locomotion. Morphological and immunoreactivity analysis and gene expression analysis were done after the completion of behavioural assessments. TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in ethanol drinking compared with stressed mice. Behavioural results showed that stress exposure induced fear and anxiety-like behaviour; however; no significant deficit was found on motor coordination, neuromuscular ability, locomotion and exploratory behaviour among groups. Morphological analysis showed no significant change in the prefrontal cortex and hippocampus among all groups, while immunoreactivity analysis showed higher expression of c-Fos in prefrontal cortex and hippocampus, higher TLR4 expression in the prefrontal cortex and glial fibrillary acidic protein (GFAP) in hippocampus among stressed-animals. Stressed-mice also showed significant increase in TLR4, Nuclear Factor-Kappa B (NF-kB), inducible nitric oxide synthase (iNOS), dopamine receptor D2 (DRD2), cyclic adenosine monophosphate (cAMP) response element binding protein-1 (CREB-1) and opioid receptor MU-1 (OPRM-1) genes expression compared with control and LPS-RS treated stressed-mice. As a conclusion, the antagonism of TLR4 could provide therapeutic value in the treatment of stress-induced addiction.

Somatic mitochondrial DNA D-loop mutations in meningioma discovered: A preliminary data.

BACKGROUND AND OBJECTIVE: Meningiomas are among the most common intracranial tumors of the central nervous system. It is widely accepted that the initiation and progression of meningiomas involve the accumulation of nucleus genetic alterations, but little is known about the implication of mitochondrial genomic alterations during development of these tumors. The human mitochondrial DNA (mtDNA) contains a short hypervariable, noncoding displacement loop control region known as the D-Loop. Alterations in the mtDNA D-loop have been reported to occur in most types of human cancers. The purpose of this study was to assess the mtDNA D-loop mutations in Malaysian meningioma patients. MATERIALS AND METHODS: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds. RESULTS: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions. CONCLUSION: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.

Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF.

INTRODUCTION: Mesenchymal stem cells (MSCs) isolated from bone marrow have different developmental origins, including neural crest. MSCs can differentiate into neural progenitor-like cells (NPCs) under the influence of bFGF and EGF. NPCs can terminally differentiate into neurons that express beta-III-tubulin and elicit action potential. The main aim of the study was to identify key genetic markers involved in differentiation of MSCs into NPCs through transcriptomic analysis. METHOD: Total RNA was isolated from MSCs and MSCs-derived NPCs followed by cDNA library construction for transcriptomic analysis. Sample libraries that passed the quality and quantity assessments were subjected to high throughput mRNA sequencing using NextSeq®500. Differential gene expression analysis was performed using the DESeq2 R package with MSC samples being a reference group. The expression of eight differentially regulated genes was counter validated using real-time PCR. RESULTS: In total, of the 3,252 differentially regulated genes between MSCs and NPCs with two or more folds, 1,771 were upregulated genes, whereas 1,481 were downregulated in NPCs. Amongst these differential genes, 104 transcription factors were upregulated, and 45 were downregulated in NPCs. Neurogenesis related genes were upregulated in NPCs and the main non-redundant gene ontology (GO) terms enriched in NPCs were the autonomic nervous system, cell surface receptor signalling pathways), extracellular structure organisation, and programmed cell death. The main non-redundant GO terms enriched in MSCs included cytoskeleton organisation cytoskeleton structural constituent, mitotic cell cycle), and the mitotic cell cycle process Gene set enrichment analysis also confirmed cell cycle regulated pathways as well as Biocarta integrin pathway were upregulated in MSCs. Transcription factors enrichment analysis by ChEA3 revealed Foxs1 and HEYL, amongst the top five transcription factors, inhibits and enhances, respectively, the NPCs differentiation of MSCs. CONCLUSIONS: The vast differences in the transcriptomic profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.

Characterization and Cellular Internalization of Spherical Cellulose Nanocrystals (CNC) into Normal and Cancerous Fibroblasts.

The aim was to isolate cellulose nanocrystals (CNC) from commercialized oil palm empty fruit bunch cellulose nanofibre (CNF) through sulphuric acid hydrolysis and explore its safeness as a potential nanocarrier. Successful extraction of CNC was confirmed through a field emission scanning electron microscope (FESEM) and attenuated total reflection Fourier transmission infrared (ATR-FTIR) spectrometry analysis. For subsequent cellular uptake study, the spherical CNC was covalently tagged with fluorescein isothiocyanate (FITC), resulting in negative charged FITC-CNC nanospheres with a dispersity (Ð) of 0.371. MTT assay revealed low degree cytotoxicity for both CNC and FITC-CNC against C6 rat glioma and NIH3T3 normal fibroblasts up to 50 µg/mL. FITC conjugation had no contribution to the particle's toxicity. Through confocal laser scanning microscope (CLSM), synthesized FITC-CNC manifested negligible cellular accumulation, indicating a poor non-selective adsorptive endocytosis into studied cells. Overall, an untargeted CNC-based nanosphere with less cytotoxicity that posed poor selectivity against normal and cancerous cells was successfully synthesized. It can be considered safe and suitable to be developed into targeted nanocarrier.

Anti-Cancer Properties of Heterotrigona itama sp. Honey Via Induction of Apoptosis in Malignant Glioma Cells.

BACKGROUND: There has been increasing evidence showing that stingless bee honey exhibits anti-oxidant, anti-inflammatory and anti-cancer properties. Pharmacologically-active components in honey such as flavonoids and phenolic constituents are known to contribute to its medicinal benefits. To the best of our knowledge, this is the first study on evaluating anti-cancer effects of locally-produced Malaysian stingless bee honey from Heterotrigona itama sp. on malignant glioma cells. METHODS: Proliferation and apoptosis studies of U-87 MG cells following stingless bee honey treatment were carried out using MTS assay and acridine orange/propidium iodide dual staining, respectively. RESULTS: Results demonstrated time and dose-dependent cytotoxicity using 0.625%, 1.25% and 10% stingless bee honey (P < 0.05). IC50 values were calculated using cells treated with 10% stingless bee honey. It was also observed that 10% stingless bee honey induced nuclear shrinkage, chromatin condensation and nucleus fragmentation, indicating that cellular changes were consistent with the apoptotic characteristics of the cells. CONCLUSION: These data provide a good basis for further evaluation of the medicinal properties of stingless bee honey from Heterotrigona itama sp. This source of honey may serve as a potential therapy for malignant glioma.

Shape-based interpolation method in measuring intracranial volume for pre- and post-operative decompressive craniectomy using open source software.

INTRODUCTION: Intracranial volume (ICV) is an important tool in the management of patients undergoing decompressive craniectomy (DC) surgery. The aim of this study was to validate ICV measurement applying the shape-based interpolation (SBI) method using open source software on computed tomography (CT) images. METHODS: The pre- and post-operative CT images of 55 patients undergoing DC surgery were analyzed. The ICV was measured by segmenting every slice of the CT images, and compared with estimated ICV calculated using the 1-in-10 sampling strategy and processed using the SBI method. An independent t test was conducted to compare the ICV measurements between the two different methods. The calculation using this method was repeated three times for reliability analysis using the intraclass correlations coefficient (ICC). The Bland-Altman plot was used to measure agreement between the methods for both pre- and post-operative ICV measurements. RESULTS: The mean ICV (±SD) were 1341.1±122.1ml (manual) and 1344.11±122.6ml (SBI) for the preoperative CT data. The mean ICV (±SD) were 1396.4±132.4ml (manual) and 1400.53±132.1ml (SBI) for the post-operative CT data. No significant difference was found in ICV measurements using the manual and the SBI methods (p=.983 for pre-op, and p=.960 for post-op). The intrarater ICC showed a significant correlation; ICC=1.00. The Bland-Altman plot showed good agreement between the manual and the SBI method. CONCLUSION: The shape-based interpolation method with 1-in-10 sampling strategy gave comparable results in estimating ICV compared to manual segmentation. Thus, this method could be used in clinical settings for rapid, reliable and repeatable ICV estimations.

Mitochondrial 10398A>G NADH-Dehydrogenase Subunit 3 of Complex I Is Frequently Altered in Intra-Axial Brain Tumors in Malaysia.

BACKGROUND: Mitochondria are major cellular sources of reactive oxygen species (ROS) generation which can induce mitochondrial DNA damage and lead to carcinogenesis. The mitochondrial 10398A>G alteration in NADH-dehydrogenase subunit 3 (ND3) can severely impair complex I, a key component of ROS production in the mitochondrial electron transport chain. Alteration in ND3 10398A>G has been reported to be linked with diverse neurodegenerative disorders and cancers. The aim of this study was to find out the association of mitochondrial ND3 10398A>G alteration in brain tumor of Malaysian patients. METHODS: Brain tumor tissues and corresponding blood specimens were obtained from 45 patients. The ND3 10398A>G alteration at target codon 114 was detected using the PCR-RFLP analysis and later was confirmed by DNA sequencing. RESULTS: Twenty-six (57.8%) patients showed ND3 10398A>G mutation in their tumor specimens, in which 26.9% of these mutations were heterozygous mutations. ND3 10398A>G mutation was not significantly correlated with age, gender, and histological tumor grade, however was found more frequently in intra-axial than in extra-axial tumors (62.5% vs. 46.2%, p<0.01). CONCLUSION: For the first time, we have been able to describe the occurrence of ND3 10398A>G mutations in a Malaysian brain tumor population. It can be concluded that mitochondrial ND3 10398A>G alteration is frequently present in brain tumors among Malaysian population and it shows an impact on the intra-axial tumors.