scholarly journals Distribution of opiate alkaloids in brain tissue of experimental animals

2012 ◽  
Vol 5 (4) ◽  
pp. 173-178 ◽  
Author(s):  
Maja Djurendic-Brenesel ◽  
Vladimir Pilija ◽  
Neda Mimica-Dukic ◽  
Branislav Budakov ◽  
Stanko Cvjeticanin
Keyword(s):  
Basal Ganglia ◽  
Brain Tissue ◽  
Regional Distribution ◽  
Opiate Receptors ◽  
Brain Regions ◽  
Gas Chromatography Mass Spectrometry ◽  
High Concentration ◽  
Experimental Animals ◽  
Female Wistar Rats ◽  
The Brain

ABSTRACT The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of μ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography-mass spectrometry (GC-MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake.

Symptoms, Related Brain Regions, and Diagnosis

2013 ◽  
Author(s):  
J. Eric Ahlskog
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Basal Ganglia ◽  
Brain Stem ◽  
Muscle Activation ◽  
Sensory Information ◽  
Brain Regions ◽  
Electrical Signal ◽  
Brain And Spinal Cord ◽  
The Brain

As a prelude to the treatment chapters that follow, we need to define and describe the types of problems and symptoms encountered in DLB and PDD. The clinical picture can be quite varied: problems encountered by one person may be quite different from those encountered by another person, and symptoms that are problematic in one individual may be minimal in another. In these disorders, the Lewy neurodegenerative process potentially affects certain nervous system regions but spares others. Affected areas include thinking and memory circuits, as well as movement (motor) function and the autonomic nervous system, which regulates primary functions such as bladder, bowel, and blood pressure control. Many other brain regions, by contrast, are spared or minimally involved, such as vision and sensation. The brain and spinal cord constitute the central nervous system. The interface between the brain and spinal cord is by way of the brain stem, as shown in Figure 4.1. Thought, memory, and reasoning are primarily organized in the thick layers of cortex overlying lower brain levels. Volitional movements, such as writing, throwing, or kicking, also emanate from the cortex and integrate with circuits just below, including those in the basal ganglia, shown in Figure 4.2. The basal ganglia includes the striatum, globus pallidus, subthalamic nucleus, and substantia nigra, as illustrated in Figure 4.2. Movement information is integrated and modulated in these basal ganglia nuclei and then transmitted down the brain stem to the spinal cord. At spinal cord levels the correct sequence of muscle activation that has been programmed is accomplished. Activated nerves from appropriate regions of the spinal cord relay the signals to the proper muscles. Sensory information from the periphery (limbs) travels in the opposite direction. How are these signals transmitted? Brain cells called neurons have long, wire-like extensions that interface with other neurons, effectively making up circuits that are slightly similar to computer circuits; this is illustrated in Figure 4.3. At the end of these wire-like extensions are tiny enlargements (terminals) that contain specific biological chemicals called neurotransmitters. Neurotransmitters are released when the electrical signal travels down that neuron to the end of that wire-like process.

scholarly journals Neuromediator systems in some brain regions of rats subjected to morphine intoxication

2010 ◽  
Vol 56 (5) ◽  
pp. 562-569
Author(s):  
S.V. Lelevich ◽  
A.A. Novokshonov
Keyword(s):  
Brain Stem ◽  
Brain Tissue ◽  
Brain Regions ◽  
Cerebral Hemispheres ◽  
Serotonin Level ◽  
Chronic Morphine ◽  
Chronic Morphine Intoxication ◽  
System Functioning ◽  
Gaba Content ◽  
The Brain

The content of neuromediators and its metabolites in the cortex of cerebral hemispheres, in thalamus and brain stem was studied under chronic morphine intoxication (7-21 days). The morphine intake during 7-14 days was accompanied by changes of catecholamine system functioning, which was the most pronounced in the thalamus and the brain stem. These changes included increased secretion of dophamine and noradrenaline, their decrease in the brain tissue, and the increased content of their metabolites. The changes of serotonin and GABA content were less pronounced and included a decrease of serotonin level and the increase of the GABA content in different periods of narcotization.

Simulation of Brain Response to Noncontact Impacts Using Coupled Eulerian–Lagrangian Method

2020 ◽  
Vol 142 (5) ◽  
Author(s):  
Miao Na ◽  
Timothy J. Beavers ◽  
Abhijit Chandra ◽  
Sarah A. Bentil
Keyword(s):  
Brain Tissue ◽  
Mechanical Response ◽  
Brain Regions ◽  
Von Mises Stress ◽  
Fe Model ◽  
Brain Response ◽  
Fe Method ◽  
Angular Velocities ◽  
Von Mises ◽  
The Brain

Abstract Finite element (FE) method has been widely used for gaining insights into the mechanical response of brain tissue during impacts. In this study, a coupled Eulerian−Lagrangian (CEL) formulation is implemented in impact simulations of a head system to overcome the mesh distortion difficulties due to large deformation in the cerebrospinal fluid (CSF) region and provide a biofidelic model of the interaction between the brain and skull. The head system used in our FE model is constructed from the transverse section of the human brain, with CSF modeled by Eulerian elements. Spring connectors are applied to represent the pia-arachnoid connection between the brain and skull. Validations of the CEL formulation and the FE model are performed using the experimental results. The dynamic response of brain tissue under noncontact impacts and the brain regions susceptible to injury are evaluated based on the intracranial pressure (ICP), maximum principal strain (MPS), and von Mises stress. While tracking the critical MPS location on the brain, higher likelihood of contrecoup injury than coup injury is found when sudden brain−skull motion takes place. The accumulation effect of CSF in the ventricle system, under large relative brain−skull motion, is also identified. The FE results show that adding relative angular velocities, to the translational impact model, not only causes a diffuse high strain area, but also cause the temporal lobes to be susceptible to cerebral contusions since the protecting CSF is prone to be squeezed away at the temporal sites due to the head rotations.

Chemical targeting of voltage sensitive dyes to specific cells and molecules in the brain

2020 ◽  
Author(s):  
Tomas Fiala ◽  
Jihang Wang ◽  
Matthew Dunn ◽  
Peter Šebej ◽  
Se Joon Choi ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Brain Tissue ◽  
Fluorescent Dyes ◽  
Brain Slices ◽  
Brain Regions ◽  
Expression Levels ◽  
Specific Targeting ◽  
The Impact ◽  
Voltage Sensitive Dyes ◽  
The Brain

Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. These sensors, rendered highly lipophilic to anchor the conjugated pi-wire molecular framework in the membrane, offer several favorable functional parameters including fast response kinetics and high sensitivity to membrane potential changes. The impact of VSDs has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a non-genetic molecular platform for cell- and molecule-specific targeting of synthetic voltage sensitive dyes in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of voltage sensitive dyes by dynamic encapsulation, and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. We envision that modularity of our platform will enable its application to a variety of molecular targets and sensors, as well as lipophilic drugs and signaling modulators. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.

Ouabain-Induced Seizures in Rats: Modification by Melatonin and Melanocyte-Stimulating Hormone

1973 ◽  
Vol 51 (8) ◽  
pp. 572-578 ◽  
Author(s):  
K. Izumi ◽  
J. Donaldson ◽  
J. Minnich ◽  
A. Barbeau
Keyword(s):  
Seizure Activity ◽  
Regional Distribution ◽  
Suppressive Effect ◽  
Young Female ◽  
Female Rats ◽  
High Accumulation ◽  
Experimental Animals ◽  
Melanocyte Stimulating Hormone ◽  
The Brain ◽  
Stimulating Hormone

The effects of melatonin and synthetic alpha-melanocyte-stimulating hormone (MSH) on ouabain-induced seizures in experimental animals were determined. Fifteen micrograms of melatonin or ten micrograms of α-MSH (dissolved in 2% ethanol – 0.85% saline) were administered intraventricularly to young female rats. The administration of melatonin was found to provide a protective effect against the seizures. The maximum suppressive effect against ouabain seizures was obtained when melatonin was given 1 min prior to the injection of ouabain. In contrast, the injection of α-MSH aggravated seizure activity elicited by 3 μg of ouabain.During experiments designed to determine the regional distribution in the brain of intraventricularly administered 3H-melatonin, high accumulation of the radioactive compound was found in the medulla oblongata – pons, the hypothalamus, and the hippocampus. The lowest activity was in the cerebral cortex.

scholarly journals Osteopontin/Secreted Phosphoprotein-1 Behaves as a Molecular Brake Regulating the Brain Translocator Protein-Dependent Neuroinflammatory Response to Chronic Viral Infection

2020 ◽  
Author(s):  
Farina J Mahmud ◽  
Yong Du ◽  
Elizabeth Greif ◽  
Thomas Boucher ◽  
Robert F Dannals ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Brain Tissue ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Brain Regions ◽  
Translocator Protein ◽  
Positron Emission ◽  
Molecular Brake ◽  
The Brain

Abstract Background Osteopontin (OPN) as a secreted signaling protein, is dramatically induced in response to cellular injury and neurodegeneration. Microglial inflammatory responses in the brain are tightly associated with the neuropathologic hallmarks of neurodegenerative disease, but understanding of the molecular mechanisms remains in several contexts, poorly understood. Methods Positron emission tomography (PET) neuroimaging using radioligands to detect increased expression of the translocator protein (TSPO) receptor in the brain, is a non-invasive tool used to track neuroinflammation in living mammals. Results In humanized, chronically HIV-infected mice in which OPN expression was knocked down with functional aptamers, uptake of TSPO radioligand, DPA-713 was markedly upregulated in the hippocampus, cortex, olfactory bulb, cerebellum and significantly increased in other key brain regions analyzed compared to controls. TSPO+ microglia were detected by immunolabeling of post-mortem brain tissue, thus validating the neuroimaging findings. Unexpectedly, two types of neurons also selectively stained positively for TSPO. The reactive cells were the specialized neurons of the cerebellum, Purkinje cells, and a subset of tyrosine hydroxylase positive neurons of the substantia nigra. Two-way ANOVA of immunoreactivity revealed that a well-validated marker of microglial activation in brain tissue, ionized calcium-binding adaptor molecule-1 (Iba-1) was significantly increased, in an interaction that depended on HIV replication. Interestingly, similar analyses of TSPO immunoreactivity showed a significant interaction with OPN expression. Conclusions Collectively, these findings using a model of chronic HIV-infection revealed for the first time two key findings: 1) two different pathways of neuroinflammation are activated, and 2) osteopontin acts as a molecular brake regulating in the brain, the inflammatory response to HIV infection.

Chemical targeting of voltage sensitive dyes to specific cells and molecules in the brain

2020 ◽  
Author(s):  
Tomas Fiala ◽  
Jihang Wang ◽  
Matthew Dunn ◽  
Peter Šebej ◽  
Se Joon Choi ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Brain Tissue ◽  
Fluorescent Dyes ◽  
Brain Slices ◽  
Brain Regions ◽  
Expression Levels ◽  
Specific Targeting ◽  
The Impact ◽  
Voltage Sensitive Dyes ◽  
The Brain

Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. These sensors, rendered highly lipophilic to anchor the conjugated pi-wire molecular framework in the membrane, offer several favorable functional parameters including fast response kinetics and high sensitivity to membrane potential changes. The impact of VSDs has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a non-genetic molecular platform for cell- and molecule-specific targeting of synthetic voltage sensitive dyes in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of voltage sensitive dyes by dynamic encapsulation, and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. We envision that modularity of our platform will enable its application to a variety of molecular targets and sensors, as well as lipophilic drugs and signaling modulators. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.

scholarly journals A Probabilistic, Distributed, Recursive Mechanism for Decision-making in the Brain

2016 ◽  
Author(s):  
Javier A. Caballero ◽  
Mark D. Humphries ◽  
Kevin N. Gurney
Keyword(s):  
Decision Making ◽  
Basal Ganglia ◽  
Neural Activity ◽  
Large Scale ◽  
Single Equation ◽  
Brain Regions ◽  
Compulsive Gambling ◽  
Choice Behaviour ◽  
Usable Information ◽  
The Brain

AbstractDecision formation recruits many brain regions, but the procedure they jointly execute is unknown. Here we characterize its essential composition, using as a framework a novel recursive Bayesian algorithm that makes decisions based on spike-trains with the statistics of those in sensory cortex (MT). Using it to simulate the random-dot-motion task, we demonstrate it quantitatively replicates the choice behaviour of monkeys, whilst predicting losses of otherwise usable information from MT. Its architecture maps to the recurrent cortico-basal-ganglia-thalamo-cortical loops, whose components are all implicated in decision-making. We show that the dynamics of its mapped computations match those of neural activity in the sensorimotor cortex and striatum during decisions, and forecast those of basal ganglia output and thalamus. This also predicts which aspects of neural dynamics are and are not part of inference. Our single-equation algorithm is probabilistic, distributed, recursive, and parallel. Its success at capturing anatomy, behaviour, and electrophysiology suggests that the mechanism implemented by the brain has these same characteristics.Author SummaryDecision-making is central to cognition. Abnormally-formed decisions characterize disorders like over-eating, Parkinson’s and Huntington’s diseases, OCD, addiction, and compulsive gambling. Yet, a unified account of decisionmaking has, hitherto, remained elusive. Here we show the essential composition of the brain’s decision mechanism by matching experimental data from monkeys making decisions, to the knowable function of a novel statistical inference algorithm. Our algorithm maps onto the large-scale architecture of decision circuits in the primate brain, replicating the monkeys’ choice behaviour and the dynamics of the neural activity that accompany it. Validated in this way, our algorithm establishes a basic framework for understanding the mechanistic ingredients of decisionmaking in the brain, and thereby, a basic platform for understanding how pathologies arise from abnormal function.

scholarly journals Kynurenines Increase MRS Metabolites in Basal Ganglia and Decrease Resting State Connectivity in Frontostriatal Reward Circuitry in Depression

2021 ◽  
Author(s):  
Xiangchuan Chen ◽  
Diana J Beltran ◽  
Valeriya D Tsygankova ◽  
Bobbi J Woolwine ◽  
Trusharth Patel ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Basal Ganglia ◽  
Magnetic Resonance ◽  
Functional Connectivity ◽  
Resting State ◽  
Animal Studies ◽  
Brain Regions ◽  
Kynurenine Pathway ◽  
Resonance Spectroscopy ◽  
The Brain

Inflammation is associated with depressive symptoms including anhedonia in patients with major depression. Nevertheless, the mechanisms by which peripheral inflammatory signals are communicated to the brain to influence central nervous system (CNS) function has yet to be fully elucidated. Based on laboratory animal studies, molecules of the kynurenine pathway (KP), which is activated by inflammation, can readily enter the brain, and generate metabolites that can alter neuronal and glial function, leading to behavioral changes. We therefore examined the relationship between KP metabolites in the plasma and cerebrospinal fluid (CSF) and brain chemistry and neural network function using multi-modal neuroimaging in 49 unmedicated, depressed subjects. CNS measures included 1) biochemical markers of glial dysfunction including glutamate (Glu) and myo-inositol (mI) in the left basal ganglia (LBG) using magnetic resonance spectroscopy (MRS); 2) local activity coherence (regional homogeneity, ReHo) and functional connectivity using resting-state functional magnetic resonance imaging; and 3) anhedonia from the Inventory for Depressive Symptoms-Self Reported. Plasma quinolinic acid (QA) was associated with increases and kynurenic acid (KYNA) and KYNA/QA with decreases in LBG Glu. Plasma kynurenine/tryptophan and CSF 3-hydroxy kynurenine (3HK) were associated with increases in LBG mI. Plasma and CSF KP were associated with decreases in ReHo in LBG and dorsomedial prefrontal cortex (DMPFC), and impaired functional connectivity between these two brain regions. DMPFC-BG connectivity mediated the effect of plasma and CSF KP metabolites on anhedonia. These findings highlight the contribution of KP metabolites to glial and neuronal dysfunction and ultimately behavior in depression.

scholarly journals Evaluation of the Oxidative Effect of Long-Term Repetitive Hyperbaric Oxygen Exposures on Different Brain Regions of Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Kemal Simsek ◽  
Mehmet Ozler ◽  
Ali Osman Yildirim ◽  
Serdar Sadir ◽  
Seref Demirbas ◽  
...  
Keyword(s):  
White Matter ◽  
Glutathione Peroxidase ◽  
Brain Tissue ◽  
Hyperbaric Oxygen ◽  
Study Groups ◽  
Brain Regions ◽  
Antioxidant Systems ◽  
Adaptive Mechanisms ◽  
The Brain

Hyperbaric oxygen (HBO2) exposure affects both oxidative and antioxidant systems. This effect is positively correlated with the exposure time and duration of the treatment. The present study aims enlightening the relation of HBO2with oxidative/antioxidant systems when administered in a prolonged and repetitive manner in brain tissues of rats. Sixty rats were divided into 6 study (n=8for each) and 1 control (n=12) group. Rats in the study groups were daily exposed 90-min HBO2sessions at 2.8 ATA for 5, 10, 15, 20, 30 and 40 days. One day after the last session, animals were sacrificed; their whole brain tissue was harvested and dissected into three different regions as the outer grey matter (cortex), the inner white matter and cerebellum. Levels of lipid peroxidation and protein oxidation and activities of superoxide dismutase and glutathione peroxidase were measured in these tissues. Malondialdehyde, carbonylated protein and glutathione peroxidase levels were found to be insignificantly increased at different time-points in the cerebral cortex, inner white matter and cerebellum, respectively. These comparable results provide evidence for the safety of HBO treatments and/or successful adaptive mechanisms at least in the brain tissue of rats, even when administered for longer periods.

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