Mental Disorders Resulting from Developmental and Mechanical Injury of the Brain Tissue.

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

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Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

Translational Neuroscience ◽

10.1515/tnsci-2020-0132 ◽

2020 ◽

Vol 11 (1) ◽

pp. 241-250

Author(s):

Zhenyu Li ◽

Guangqian Ding ◽

Yudi Wang ◽

Zelong Zheng ◽

Jianping Lv

Keyword(s):

Gene Therapy ◽

Transcription Factor ◽

Neurodegenerative Diseases ◽

Brain Tissue ◽

Inflammatory Responses ◽

Tissue Samples ◽

Protein Levels ◽

Virus Serotype ◽

Transcription Factor Eb ◽

The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

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High-fat diet-induced obesity and impairment of brain neurotransmitter pool

Translational Neuroscience ◽

10.1515/tnsci-2020-0099 ◽

2020 ◽

Vol 11 (1) ◽

pp. 147-160

Author(s):

Ranyah Shaker M. Labban ◽

Hanan Alfawaz ◽

Ahmed T. Almnaizel ◽

Wail M. Hassan ◽

Ramesa Shafi Bhat ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Tissue ◽

High Fat Diet ◽

Density Lipoprotein ◽

Obese Group ◽

Control Group ◽

High Fat ◽

Brain Neurotransmitter ◽

The Brain ◽

Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

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Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats

Brain Sciences ◽

10.3390/brainsci11070889 ◽

2021 ◽

Vol 11 (7) ◽

pp. 889

Author(s):

Anton D. Filev ◽

Denis N. Silachev ◽

Ivan A. Ryzhkov ◽

Konstantin N. Lapin ◽

Anastasiya S. Babkina ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Tissue ◽

Target Genes ◽

Neural Function ◽

Stress Genes ◽

Expression Of Genes ◽

Delayed Recovery ◽

The Brain ◽

Lower Expression

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

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Pyruvic acid as an intermediary metabolite in the brain tissue of avitaminous and normal pigeons

Biochemical Journal ◽

10.1042/bj0280916 ◽

1934 ◽

Vol 28 (3) ◽

pp. 916-925 ◽

Cited By ~ 55

Author(s):

Rudolph Albert Peters ◽

Robert Henry Stewart Thompson

Keyword(s):

Brain Tissue ◽

Pyruvic Acid ◽

Intermediary Metabolite ◽

The Brain

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EXPERIMENTS ON THE SURVIVAL OF THE FEBRILE HERPETIC AND ALLIED VIRUSES IN VITRO

Journal of Experimental Medicine ◽

10.1084/jem.39.4.533 ◽

1924 ◽

Vol 39 (4) ◽

pp. 533-542 ◽

Cited By ~ 4

Author(s):

James E. McCartney

Keyword(s):

Brain Tissue ◽

Secondary Infection ◽

The Body ◽

Herpes Viruses ◽

Encephalitis Lethargica ◽

Aerobic Conditions ◽

Maximum Period ◽

Suitable Technique ◽

The Brain

These studies fail to confirm the statements previously made that microorganisms of the class of the globoid bodies of poliomyelitis may be cultivated in the Smith-Noguchi medium from the so called virus of encephalitis lethargica. They show equally that the herpes virus does not multiply in this medium. The experiments indicate, moreover, that the medium is unfavorable to the survival of the virus, while ordinary broth under aerobic conditions is more favorable for maintaining the activity of both the encephalitic and the herpes viruses. Probably no multiplication of either takes place in the latter medium but merely a survival, and for a maximum period of 6 days in the broth itself, and 12 days in the fragment of brain tissue immersed in the broth. Finally, it has been shown that with a suitable technique the viruses can be passed from the brain of one rabbit to that of another through a long series without contamination with cocci or other common bacterial forms. Hence we regard all reports of the finding of ordinary bacteria in the brain of cases of epidemic or lethargic encephalitis as instances of mixed or secondary infection arising during life, or examples of postmortem invasion of the body, or of faulty technique at the autopsy.

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Protective effect of Saccharomyces cerevisiae in Rattus norvegicus Ischemic Stroke Model

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.01006 ◽

2021 ◽

pp. 5785-5789

Author(s):

Dedy Budi Kurniawan ◽

Mokhamad Fahmi Rizki Syaban ◽

Arinal Mufidah ◽

Muhammad Unzila Rafsi Zulfikri ◽

Wibi Riawan

Keyword(s):

Saccharomyces Cerevisiae ◽

Ischemic Stroke ◽

Brain Tissue ◽

Tissue Injury ◽

Intervention Group ◽

Positive Control ◽

Positive Control Group ◽

Control Group ◽

Hematopoietic Stem ◽

The Brain

Stroke is one of the leading causes of morbidity and mortality in all ages. Ischemic stroke activates excitotoxic glutamate cascade leading to brain tissue injury. Saccharomyces cerevisiae is a unicellular yeast widely found in nature. S. cerevisiae is neuroprotective and able to increase the differentiation of hematopoietic stem cells (HSCs) into neuronal cells. it may increase levels of neuroprotectant BDNF in the brain tissue, therefore increase the protection of neurons. BDNF may prevent glutamate-driven excitotoxicity by reducing glutamate levels. This study uses a randomized post-test only controlled group design. In this in vivo study, rodent models of ischemic stroke were divided into five groups comprising of the negative control group, positive control group, intervention group 1 (18mg/kgBW), intervention group 2 (36mg/kgBW) and intervention group 3 (72 mg/kgBW). Groups treated with Saccharomyces cerevisiae extract showed significantly increased BDNF levels in the brain tissue, and the expression of the glutamate level was significantly reduced (P <0.05) compared to the positive control group. Thus Saccharomyces cerevisiae has a promising potential to become a therapy against ischemic stroke disease. however further research is needed regarding the efficacy and toxicity of Saccharomyces cerevisiae.

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Expression of NMDA receptor and microRNA-219 in rats submitted to cerebral ischemia associated with alcoholism

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20160188 ◽

2017 ◽

Vol 75 (1) ◽

pp. 30-35 ◽

Cited By ~ 1

Author(s):

Cristiane Iozzi Silva ◽

Paulo Cézar Novais ◽

Andressa Romualdo Rodrigues ◽

Camila A.M. Carvalho ◽

Benedicto Oscar Colli ◽

...

Keyword(s):

Gene Expression ◽

Cerebral Ischemia ◽

Brain Tissue ◽

Wistar Rats ◽

Molecular Mechanisms ◽

Inverse Correlation ◽

Control Group ◽

The Brain ◽

Lower Expression ◽

Control Sham

ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.

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Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain

Frontiers in Neuroanatomy ◽

10.3389/fnana.2021.767223 ◽

2021 ◽

Vol 15 ◽

Author(s):

Miriam Menzel ◽

Marouan Ritzkowski ◽

Jan A. Reuter ◽

David Gräßel ◽

Katrin Amunts ◽

...

Keyword(s):

Human Brain ◽

Nerve Fiber ◽

Brain Tissue ◽

Scattered Light ◽

Polar Angle ◽

Nerve Fibers ◽

Fiber Architecture ◽

Whole Brain ◽

Tissue Samples ◽

The Brain

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

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