Immunohistochemical analysis of GFAP expression in the experimental sepsis-associated encephalopathy

Pathophysiology of sepsis-associated encephalopathy (SAE) is linked to blood-brain barrier breakdown, neuroinflammation and neurotransmitter imbalance in the brain. Astroglia, the most abundant cell population within the brain, plays the critical role in control of all kinds of homeostatic processes, thereby regulating the adaptive reactions of the brain to various challenges. Astroglia are highly heterogenous across the brain regions, therefore, damaging factors stimulate heterogenous astroglial reactivity and response in different brain regions. The aim of this study was determining immunohistochemical features of GFAP expression in various brain regions in the model of rodent experimental sepsis. Materials and methods. The experiment was performed in Wistar rats: control group of 5 sham-operated rats and the main group of 20 rats subjected to cecum ligation and puncture (CLP) procedure. The immunohistochemical study of GFAP expression in the sensorimotor cortex, subcortical white matter, hippocampal, thalamic and caudate nucleus/putamen regions was performed from 20 to 48 hours of the postoperative period. Results. Starting from the 12th hour after CLP, animals began display progressive increase in signs of periorbital exudation, piloerection, fever-/hypothermia, diarrhea, social isolation, lethargy, and respiratory impairment. In the period of 20–38 hours, 9 animals showed expressed previously listed symptoms and were euthanized (CLP-B – lethal group), 11 rats survived until 48 hours of the experiment (CLP-A – survived group). In the lethal group, starting from 20 to 38 hours after the CLP procedure, a significant (relative to control) regionally-specific dynamic increase in the level of GFAP expression was observed in the brain: in the cortex – by 465 %, in the subcortical white matter – by 198 %, in the hippocampus – by 250 %, from the 23rd hour – in the caudate nucleus/putamen by 18 %. In the thalamus, no significant changes in the level of GFAP expression were observed. In the cortex and hippocampus of survived animals, 48 h after CLP, higher values of GFAP expression were observed comparing to the group of non-survived animals. Conclusions. Under conditions of the experimental SAE, an early dynamic increase in the astroglial reactivity was observed in the cortex, hippocampus, white matter, and caudate nucleus/putamen of the brain with the most significant increase of indicators in the cortex and hippocampus, which potentially indicates relatively more vulnerable areas of the brain to damaging factors, as well as places of the most active intercellular interaction in the condition of systemic inflammation. Higher values of GFAP expression in the cortex and hippocampus of survived animals at 48 hours of the experiment, compared with indicators of non-survived group, indicate increased astroglial reactivity in these brain regions at the noted time period, accompanied by relatively more favorable clinical course of the disease.

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Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study)

Journal of Education, Health and Sport ◽

10.12775/jehs.2021.11.10.033 ◽

2021 ◽

Vol 11 (10) ◽

pp. 342-356

Author(s):

T. Shulyatnikova ◽

V. Tumanskiy

Keyword(s):

White Matter ◽

Glutamine Synthetase ◽

Liver Failure ◽

Acute Liver Failure ◽

Caudate Nucleus ◽

Immunohistochemical Study ◽

Clinical Signs ◽

Brain Regions ◽

Progressive Increase ◽

The Brain

The aim of the study was to determine the immunohistochemical level of glutamine synthetase (GS) expression in different brain regions in the conditions of experimental acute liver failure in rats. Materials and methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GS expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen was carried out in the period of 12-24 h after acetaminophen treatment. Results. Beginning from the 6th hour after acetaminophen treatment all AILF-animals showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h - they constituted subgroup AILF-B, “non-survived”. 4 animals survived until the 24 h - subgroup AILF-A, “survived”. In the AILF-B group, starting from 16 to 24 hours after treatment, a significant (relative to control) regionally-specific dynamic increase in the level of GS expression was observed in the brain: in the cortex – by 307.33 %, in the thalamus – by 249.47%, in the hippocampus – by 245.53%, in the subcortical white matter – by 126.08%, from 12th hour – in the caudate nucleus/putamen, by 191.66 %; with the most substantive elevation of GS expression in the cortex: by 4.07 times. Conclusion. Starting from the 16th hours after the acetaminophen treatment (from the 12th h in the caudate nucleus/putamen region) and up to 24 h, it is observed reliable compared to control dynamic increase in GS protein expression in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen of the rat brain with the most significant elevation in the cortex among other regions. The heterogeneity in the degree of GS expression rising in different brain regions potentially may indicate regions more permeable for ammonia and/or other systemic toxic factors as well as heterogeneous sensitivity of brain regions to deleterious agents in conditions of AILF. Subsequently, revealed diversity in the GS expression reflects the specificity of reactive response of local astroglia in the condition of AILF-encephalopathy during specific time-period. The dynamic increase in the GS expression associated with impairment of animal state, indicates involvement of increased GS levels in the mechanisms of experimental acute hepatic encephalopathy.

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What Has Direct Cortical and Subcortical Electrostimulation Taught Us about Neurolinguistics?

The Oxford Handbook of Neurolinguistics ◽

10.1093/oxfordhb/9780190672027.013.8 ◽

2019 ◽

pp. 185-211

Author(s):

Hugues Duffau

Keyword(s):

White Matter ◽

Large Scale ◽

Functional Neuroimaging ◽

Great Accuracy ◽

Subcortical White Matter ◽

Cerebral Lesions ◽

Physiological Basis ◽

Postoperative Mri ◽

The Brain

Investigating the neural and physiological basis of language is one of the most important challenges in neurosciences. Direct electrical stimulation (DES), usually performed in awake patients during surgery for cerebral lesions, is a reliable tool for detecting both cortical and subcortical (white matter and deep grey nuclei) regions crucial for cognitive functions, especially language. DES transiently interacts locally with a small cortical or axonal site, but also nonlocally, as the focal perturbation will disrupt the entire subnetwork sustaining a given function. Thus, in contrast to functional neuroimaging, DES represents a unique opportunity to identify with great accuracy and reproducibility, in vivo in humans, the structures that are actually indispensable to the function, by inducing a transient virtual lesion based on the inhibition of a subcircuit lasting a few seconds. Currently, this is the sole technique that is able to directly investigate the functional role of white matter tracts in humans. Thus, combining transient disturbances elicited by DES with the anatomical data provided by pre- and postoperative MRI enables to achieve reliable anatomo-functional correlations, supporting a network organization of the brain, and leading to the reappraisal of models of language representation. Finally, combining serial peri-operative functional neuroimaging and online intraoperative DES allows the study of mechanisms underlying neuroplasticity. This chapter critically reviews the basic principles of DES, its advantages and limitations, and what DES can reveal about the neural foundations of language, that is, the large-scale distribution of language areas in the brain, their connectivity, and their ability to reorganize.

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Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

International Journal of Molecular Sciences ◽

10.3390/ijms22094953 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4953

Author(s):

Natalie M. Zahr ◽

Kilian M. Pohl ◽

Allison J. Kwong ◽

Edith V. Sullivan ◽

Adolf Pfefferbaum

Keyword(s):

White Matter ◽

Proinflammatory Cytokines ◽

Soluble Protein ◽

Subcortical White Matter ◽

Control Group ◽

White Matter Volume ◽

Brain Volumes ◽

Protein Levels ◽

Matter Volume ◽

Patient Groups

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

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IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function

Experimental Biology and Medicine ◽

10.1177/153537020523000503 ◽

2005 ◽

Vol 230 (5) ◽

pp. 292-306 ◽

Cited By ~ 90

Author(s):

Shabrine S. Daftary ◽

Andrea C. Gore

Keyword(s):

Critical Role ◽

Somatic Growth ◽

Reproductive Function ◽

Brain Regions ◽

Pituitary Hormones ◽

Somatotropic Axis ◽

Gnrh Neurons ◽

Close Relationship ◽

The Brain ◽

Neuroendocrine Functions

Given the close relationship among neuroendocrine systems, it Is likely that there may be common signals that coordinate the acquisition of adult reproductive function with other homeo-static processes. In this review, we focus on central nervous system insulin-like growth factor-1 (IGF-1) as a signal controlling reproductive function, with possible links to somatic growth, particularly during puberty. In vertebrates, the appropriate neurosecretion of the decapeptide gonadotropin-releas-ing hormone (GnRH) plays a critical role in the progression of puberty. Gonadotropin-releasing hormone is released in pulses from neuroterminals in the median eminence (ME), and each GnRH pulse triggers the production of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These pituitary hormones in turn stimulate the synthesis and release of sex steroids by the gonads. Any factor that affects GnRH or gonadotropin pulsatility is important for puberty and reproductive function and, among these factors, the neurotrophic factor IGF-1 is a strong candidate. Although IGF-1 is most commonly studied as the tertiary peripheral hormone in the somatotropic axis via its synthesis in the liver, IGF-1 Is also synthesIzed in the brain, within neurons and glia. In neuroendocrine brain regions, central IGF-1 plays roles in the regulation of neuroendocrine functions, including direct actions on GnRH neurons. Moreover, GnRH neurons themselves co-express IGF-1 and the IGF-1 receptor, and this expression is developmentally regulated. Here, we examine the role of IGF-1 acting in the hypothalamus as a critical link between reproductive and other neuroendocrine functions.

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Microsurgical anatomy of the central core of the brain

Journal of Neurosurgery ◽

10.3171/2017.5.jns162897 ◽

2018 ◽

Vol 129 (3) ◽

pp. 752-769 ◽

Cited By ~ 13

Author(s):

Eduardo Carvalhal Ribas ◽

Kaan Yağmurlu ◽

Evandro de Oliveira ◽

Guilherme Carvalhal Ribas ◽

Albert Rhoton

Keyword(s):

White Matter ◽

Caudate Nucleus ◽

Internal Capsule ◽

Central Core ◽

Surgical Approaches ◽

Microsurgical Anatomy ◽

Functional Importance ◽

Posterior Portion ◽

External Capsule ◽

The Brain

OBJECTIVEThe purpose of this study was to describe in detail the cortical and subcortical anatomy of the central core of the brain, defining its limits, with particular attention to the topography and relationships of the thalamus, basal ganglia, and related white matter pathways and vessels.METHODSThe authors studied 19 cerebral hemispheres. The vascular systems of all of the specimens were injected with colored silicone, and the specimens were then frozen for at least 1 month to facilitate identification of individual fiber tracts. The dissections were performed in a stepwise manner, locating each gray matter nucleus and white matter pathway at different depths inside the central core. The course of fiber pathways was also noted in relation to the insular limiting sulci.RESULTSThe insular surface is the most superficial aspect of the central core and is divided by a central sulcus into an anterior portion, usually containing 3 short gyri, and a posterior portion, with 2 long gyri. It is bounded by the anterior limiting sulcus, the superior limiting sulcus, and the inferior limiting sulcus. The extreme capsule is directly underneath the insular surface and is composed of short association fibers that extend toward all the opercula. The claustrum lies deep to the extreme capsule, and the external capsule is found medial to it. Three fiber pathways contribute to form both the extreme and external capsules, and they lie in a sequential anteroposterior disposition: the uncinate fascicle, the inferior fronto-occipital fascicle, and claustrocortical fibers. The putamen and the globus pallidus are between the external capsule, laterally, and the internal capsule, medially. The internal capsule is present medial to almost all insular limiting sulci and most of the insular surface, but not to their most anteroinferior portions. This anteroinferior portion of the central core has a more complex anatomy and is distinguished in this paper as the “anterior perforated substance region.” The caudate nucleus and thalamus lie medial to the internal capsule, as the most medial structures of the central core. While the anterior half of the central core is related to the head of the caudate nucleus, the posterior half is related to the thalamus, and hence to each associated portion of the internal capsule between these structures and the insular surface. The central core stands on top of the brainstem. The brainstem and central core are connected by several white matter pathways and are not separated from each other by any natural division. The authors propose a subdivision of the central core into quadrants and describe each in detail. The functional importance of each structure is highlighted, and surgical approaches are suggested for each quadrant of the central core.CONCLUSIONSAs a general rule, the internal capsule and its vascularization should be seen as a parasagittal barrier with great functional importance. This is of particular importance in choosing surgical approaches within this region.

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Cortical activation in alexithymia as a response to emotional stimuli

The British Journal of Psychiatry ◽

10.1192/bjp.bp.106.034728 ◽

2008 ◽

Vol 192 (1) ◽

pp. 32-38 ◽

Cited By ~ 74

Author(s):

Hasse Karlsson ◽

Petri Näätänen ◽

Hanna Stenman

Keyword(s):

Emotion Processing ◽

Three Dimensional ◽

Brain Regions ◽

Physical Symptoms ◽

Cortical Activation ◽

Anterior Cingulate ◽

Control Group ◽

Emotional Stimuli ◽

Healthy Women ◽

The Brain

BackgroundAlexithymia has been shown to be related to many psychiatric and somatic illnesses. Aberrant emotion processing in the brain may underlie several psychiatric disorders. However, little is known about the neurobiological underpinnings of alexithymia.AimsTo determine the way in which the brain processes emotion in alexithymia.MethodThe participants were 10 healthy women with alexithymia and 11 healthy women without this condition, recruited into the study on the basis of their scores on the 20-item Toronto Alexithymia Scale. Four films were projected on a video screen to induce each of three emotional conditions (neutral, amusement, sadness). The brain areas activated during emotional stimuli in the alexithymia group were compared with those activated in the non-alexithymia group. Scans of the distribution of [15O]H2O were acquired using a positron emission tomography (PET) scanner operated in three-dimensional mode.ResultsIn response to emotional stimuli participants with alexithymia activated more parts of their sensory and motor cortices and insula, especially on the left side, and less of their anterior cingulate, compared with the control group.ConclusionsWomen with alexithymia seem to over-activate their ‘bodily’ brain regions, implying a different mode of emotion processing. This may be related to their tendency to experience physical symptoms.

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Evidence of increased brain amyloid in severe TBI survivors at 1, 12, and 24 months after injury: report of 2 cases

Journal of Neurosurgery ◽

10.3171/2015.6.jns15639 ◽

2016 ◽

Vol 124 (6) ◽

pp. 1646-1653 ◽

Cited By ~ 12

Author(s):

Joshua W. Gatson ◽

Cari Stebbins ◽

Dana Mathews ◽

Thomas S. Harris ◽

Christopher Madden ◽

...

Keyword(s):

Caudate Nucleus ◽

Pet Imaging ◽

Rating Scale ◽

Occipital Cortex ◽

Standard Uptake Value ◽

Severe Trauma ◽

Brain Regions ◽

Severe Tbi ◽

The Brain ◽

Time Point

Traumatic brain injury (TBI) is a major risk factor for Alzheimer’s disease. With respect to amyloid deposition, there are no published serial data regarding the deposition rate of amyloid throughout the brain after TBI. The authors conducted serial 18F-AV-45 (florbetapir F18) positron emission tomography (PET) imaging in 2 patients with severe TBI at 1, 12, and 24 months after injury. A total of 12 brain regions were surveyed for changes in amyloid levels. Case 1 involved a 50-year-old man who experienced a severe TBI. Compared with the 1-month time point, of the 12 brain regions that were surveyed, a decrease in amyloid (as indicated by standard uptake value ratios) was only observed in the hippocampus (−16%, left; −12%, right) and caudate nucleus (−18%, left; −18%, right), suggesting that initial amyloid accumulation in the brain was cleared between time points 1 and 12 months after injury. Compared to the scan at 1 year, a greater increase in amyloid (+15%) was observed in the right hippocampus at the 24-month time point. The patient in Case 2 was a 37-year-old man who suffered severe trauma to the head and a subsequent stroke; he had poor cognitive/functional outcomes and underwent 1.5 years of rehabilitation. Due to a large infarct area on the injured side of the brain (right side), the authors focused primarily on brain regions affected within the left hemisphere. Compared with the 1-month scan, they only found an increase in brain amyloid within the left anterior putamen (+11%) at 12 months after injury. In contrast, decreased amyloid burden was detected in the left caudate nucleus (−48%), occipital cortex (−21%), and precuneus (−19%) brain regions at the 12-month time point, which is indicative of early accumulation and subsequent clearance. In comparison with 12-month values, more clearance was observed, since a reduction in amyloid was found at 24 months after trauma within the left anterior putamen (−12%) and occipital cortex (−15%). Also, by 24 months, most of the amyloid had been cleared and the patient demonstrated improved results on the Rivermead symptom questionnaire, Glasgow Outcome Scale-Extended, and Disability Rating Scale. With respect to APOE status, the patient in Case 1 had two ε3 alleles and the patient in Case 2 had one ε2 and one ε3 allele. In comparison to the findings of the initial scan at 1 month after TBI, by 12 and 24 months after injury amyloid was cleared in some brain regions and increased in others. Serial imaging conducted here suggests that florbetapir F18 PET imaging may be useful in monitoring amyloid dynamics within specific brain regions following severe TBI and may be predictive of cognitive deficits.

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The Value of Diffusion Kurtosis Imaging In Detecting Delayed Brain Development of Premature Infants

10.21203/rs.3.rs-747810/v1 ◽

2021 ◽

Author(s):

Xin Zhao ◽

Chunxiang Zhang ◽

Bohao Zhang ◽

Jiayue Yan ◽

Kaiyu Wang ◽

...

Keyword(s):

White Matter ◽

Caudate Nucleus ◽

Premature Infants ◽

Developmental Disorders ◽

Neurodevelopmental Outcome ◽

Mean Diffusivity ◽

Internal Capsule ◽

Diffusion Kurtosis Imaging ◽

Control Group ◽

Diffusion Kurtosis

Abstract Objective Preterm infants are at high risk of adverse neurodevelopmental outcome. Our aim is to explore the value of diffusion kurtosis imaging (DKI) in diagnosing brain developmental disorders in premature infants.Materials and Methods A total of 52 subjects were included in this study, including 26 premature infants as the preterm group, and 26 full-term infants as the control group. Routine magnetic resonance imaging and DKI examination were performed. Mean kurtosis (MK), radial kurtosis (RK), fractional anisotropy (FA), mean diffusivity (MD) values were measured in the brain regions including posterior limbs of the internal capsule (PLIC); anterior limb of internal capsule (ALIC); parietal white matter (PWM); frontal white matter (FWM); thalamus (TH); caudate nucleus (CN); genu of the corpus callosum (GCC). The X2, t test, Spearman’s correlation analysis and receiver operating characteristic curve (ROC)were used for data analyses.Results In the premature infant group, the MK and RK values of PLIA, ALIC, and PWM were lower than those in the control group (P<0.05). The FA values of PWM, FWM and TH were also lower than those of the control group (P<0.05). The AUCs of MK in PLIC and ALIC, MD in PWM, and FA in FWM were 0.813, 0.802, 0.842 and 0.867 (P<0.05). In thalamus and caudate nucleus, the correlations between MK, RK values and PMA were higher than those between FA, MD values and PMA.Conclusions DKI can be used as an effective tool in detecting brain developmental disorders in premature infants.

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Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats

Journal of Veterinary Research ◽

10.2478/jvetres-2019-0027 ◽

2019 ◽

Vol 63 (2) ◽

pp. 285-292

Author(s):

Ning Ma ◽

Xin Li ◽

Hong-bin Wang ◽

Li Gao ◽

Jian-hua Xiao

Keyword(s):

Mrna Expression ◽

Opposite Effect ◽

Brain Regions ◽

Control Group ◽

Sprague Dawley ◽

Sd Rats ◽

The Central Nervous System ◽

Specific Antagonist ◽

Sedation And Analgesia ◽

The Brain

AbstractIntroduction:Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.Material and Methods:A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR.Results:XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas.Conclusion:XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

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Functionnectome: a framework to analyse the contribution of brain circuits to fMRI

10.21203/rs.3.rs-129060/v1 ◽

2021 ◽

Author(s):

Victor Nozais ◽

Stephanie Forkel ◽

Chris Foulon ◽

Laurent Petit ◽

Michel Thiebaut de Schotten

Keyword(s):

White Matter ◽

Functional Neuroimaging ◽

Brain Regions ◽

Functional Networks ◽

Language Functions ◽

Brain Circuits ◽

Novel Method ◽

Joint Contribution ◽

The Relationship ◽

The Brain

Abstract In recent years, the field of functional neuroimaging has moved from a pure localisationist approach of isolated functional brain regions to a more integrated view of those regions within functional networks. The methods used to investigate such networks, however, rely on local signals in grey matter and are limited in identifying anatomical circuitries supporting the interaction between brain regions. Mapping the brain circuits mediating the functional signal between brain regions would propel forward our understanding of the brain’s functional signatures and dysfunctions. We developed a novel method to unravel the relationship between brain circuits and functions: The Functionnectome. The Functionectome combines the functional signal from fMRI with the anatomy of white matter brain circuits to unlock and chart the first maps of functional white matter. To showcase the versatility of this new method, we provide the first functional white matter maps revealing the joint contribution of connected areas to motor, working memory, and language functions. The Functionnectome comes with an open source companion software and opens new avenues into studying functional networks by applying the method to already existing dataset and beyond task fMRI.

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