scholarly journals Cognitive impairment in patients with migraine: causes, principles of effective prevention and treatment

2018 ◽  
Vol 10 (3) ◽  
pp. 141-149
Author(s):  
V. A. Golovacheva ◽  
K. A. Pozhidaev ◽  
A. A. Golovacheva
Keyword(s):  
Clinical Trials ◽  
Cognitive Impairment ◽  
Anxiety Disorder ◽  
White Matter ◽  
Effective Prevention ◽  
Pathogenetic Role ◽  
Brain White Matter ◽  
Prevention And Treatment ◽  
The Brain

Cognitive impairment (CI) is common in patients with migraine; its causes and pathogenesis continue to be discussed. Some authors consider that migraine proper does not lead to decreased cognitive functions, neuroimaging changes in the brain white matter are asymptomatic in migraine; and CI in patients with this condition is caused by comorbidities (depression, anxiety disorder) and/or concurrent cerebrovascular and neurodegenerative diseases. Other authors report the pathogenetic role of migraine in the development of CI and the importance of the frequency of headache attacks and neuroimaging changes in the brain matter in migraine. The paper reviews clinical trials dealing with the prevalence, causes, and pathogenesis of CI in patients with migraine. It sets forth the current principles of prevention and treatment of CI in patients with this condition.

scholarly journals Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

2018 ◽  
Author(s):  
Miho Sato-Hashimoto ◽  
Tomomi Nozu ◽  
Riho Toriba ◽  
Ayano Horikoshi ◽  
Miho Akaike ◽  
...  
Keyword(s):  
White Matter ◽  
Membrane Protein ◽  
Functional Role ◽  
Regulatory Protein ◽  
Genetic Ablation ◽  
Brain White Matter ◽  
Expression Of Genes ◽  
The Brain ◽  
Repair Phase

AbstractA characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

Protective Role of Levetiracetam Against Cognitive Impairment And Brain White Matter Damage in Mouse prolonged Cerebral Hypoperfusion

Neuroscience ◽  
2019 ◽  
Vol 414 ◽  
pp. 255-264 ◽  
Author(s):  
Toshiki Inaba ◽  
Nobukazu Miyamoto ◽  
Kenichiro Hira ◽  
Yuji Ueno ◽  
Kazuo Yamashiro ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Protective Role ◽  
Cerebral Hypoperfusion ◽  
White Matter Damage ◽  
Brain White Matter

scholarly journals Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice

2019 ◽  
Vol 40 (8) ◽  
pp. 1709-1723 ◽  
Author(s):  
Laurent Suissa ◽  
Virginie Flachon ◽  
Jean-Marie Guigonis ◽  
Charles-Vivien Olivieri ◽  
Fanny Burel-Vandenbos ◽  
...  
Keyword(s):  
White Matter ◽  
Single Photon ◽  
Photon Emission ◽  
Brain White Matter ◽  
Single Photon Emission Ct ◽  
Altered Glucose ◽  
Intramyelinic Oedema ◽  
The Brain ◽  
Deficient Mice

SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone β-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.

MicroRNAs participate in the regulation of oligodendrocytes development in white matter injury

2018 ◽  
Vol 29 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Dongqiong Xiao ◽  
Yi Qu ◽  
Lingli Pan ◽  
Xihong Li ◽  
Dezhi Mu
Keyword(s):  
Cerebral Palsy ◽  
Cognitive Impairment ◽  
White Matter ◽  
Behavioral Disorders ◽  
White Matter Injury ◽  
New Agents ◽  
Brain White Matter ◽  
Prevention And Treatment ◽  
Molecular Etiology ◽  
Made In

AbstractWhite matter injury (WMI) often results in cognitive impairment, behavioral disorders, and cerebral palsy and thus imposes a tremendous burden on society. The cells in brain white matter mainly comprise oligodendrocytes (OLs), astrocytes, and microglia. The dysregulation of OLs development is the pathological hallmark of WMI. Recent studies have demonstrated that microRNAs (miRNAs or miRs) participate in the regulation of OLs development, and the dysregulation of this process represents the pathogenesis of WMI. This review summarizes the progress made in this field that will help clinicians and researchers understand the molecular etiology of WMI and develop miRNAs as new agents for the prevention and treatment of WMI.

scholarly journals Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Miho Sato-Hashimoto ◽  
Tomomi Nozu ◽  
Riho Toriba ◽  
Ayano Horikoshi ◽  
Miho Akaike ◽  
...  
Keyword(s):  
White Matter ◽  
Membrane Protein ◽  
Functional Role ◽  
Regulatory Protein ◽  
Genetic Ablation ◽  
Brain White Matter ◽  
Expression Of Genes ◽  
The Brain ◽  
Repair Phase

A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

scholarly journals Protein farnesylation is upregulated in Alzheimer’s human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer’s model mice

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Angela Jeong ◽  
Shaowu Cheng ◽  
Rui Zhong ◽  
David A. Bennett ◽  
Martin O. Bergö ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Gtpases ◽  
Specific Role ◽  
Postmortem Brain ◽  
Effective Prevention ◽  
Postmortem Brain Tissue ◽  
Mtorc1 Signaling ◽  
Behavioral Assessments ◽  
Human Brains

AbstractThe pathogenic mechanisms underlying the development of Alzheimer’s disease (AD) remain elusive and to date there are no effective prevention or treatment for AD. Farnesyltransferase (FT) catalyzes a key posttranslational modification process called farnesylation, in which the isoprenoid farnesyl pyrophosphate is attached to target proteins, facilitating their membrane localization and their interactions with downstream effectors. Farnesylated proteins, including the Ras superfamily of small GTPases, are involved in regulating diverse physiological and pathological processes. Emerging evidence suggests that isoprenoids and farnesylated proteins may play an important role in the pathogenesis of AD. However, the dynamics of FT and protein farnesylation in human brains and the specific role of neuronal FT in the pathogenic progression of AD are not known. Here, using postmortem brain tissue from individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), or Alzheimer’s dementia, we found that the levels of FT and membrane-associated H-Ras, an exclusively farnesylated protein, and its downstream effector ERK were markedly increased in AD and MCI compared with NCI. To elucidate the specific role of neuronal FT in AD pathogenesis, we generated the transgenic AD model APP/PS1 mice with forebrain neuron-specific FT knockout, followed by a battery of behavioral assessments, biochemical assays, and unbiased transcriptomic analysis. Our results showed that the neuronal FT deletion mitigates memory impairment and amyloid neuropathology in APP/PS1 mice through suppressing amyloid generation and reversing the pathogenic hyperactivation of mTORC1 signaling. These findings suggest that aberrant upregulation of protein farnesylation is an early driving force in the pathogenic cascade of AD and that targeting FT or its downstream signaling pathways presents a viable therapeutic strategy against AD.

Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments

2006 ◽  
Vol 18 (5) ◽  
pp. 193-209 ◽  
Author(s):  
Richard J. Porter ◽  
Peter Gallagher
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Impairment ◽  
Hpa Axis ◽  
Affective Disorders ◽  
Psychotic Depression ◽  
Review Of The Literature ◽  
Hpa Axis Dysregulation ◽  
New Evidence ◽  
The Brain

Background:New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed.Objective:To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone.Method:A selective review of the literature.Results:The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments.Conclusion:Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.

Sleep and Violence*

1984 ◽  
Vol 29 (2) ◽  
pp. 132-134 ◽  
Author(s):  
L.B. Raschka
Keyword(s):  
Differential Diagnosis ◽  
Sleep Apnea ◽  
Central Sleep Apnea ◽  
Upper Airway ◽  
Violent Behaviour ◽  
Car Accidents ◽  
Prevention And Treatment ◽  
Respiratory Pathology ◽  
The Brain

Most violence connected with sleep disorder is assumed to be related to sleep walking. It is less well known that other sleep disorders can also give rise to violence. The role of narcolepsy in car accidents is mentioned. Sleep drunkenness can lead to confusion resulting in violent behaviour especially on forced awakening. This condition is associated to sleep apnea. Primary or central sleep apnea is caused by disorders of the brain stem affecting the respiratory center. Secondary or upper airway sleep apnea can be caused by virtually any condition that results in cessation of the airflow due to occlusion of the upper airway. The author describes one patient who engaged in assaultive behaviour on forced awakening following earlier alcohol consumption. The pathomechanism of violent behaviour generated by a combination of sleep apnea and respiratory pathology is described. The differential diagnosis, prevention and treatment is outlined. The use of polysomnography in diagnosis and the potentially dangerous effects of drugs with respiratory depressing effects is highlighted.

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

On the microstructural origin of brain white matter hydraulic permeability

2021 ◽  
Vol 118 (36) ◽  
pp. e2105328118
Author(s):  
Marco Vidotto ◽  
Andrea Bernardini ◽  
Marco Trovatelli ◽  
Elena De Momi ◽  
Daniele Dini
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Drug Transport ◽  
Three Dimensional ◽  
Principal Component ◽  
Hydraulic Permeability ◽  
Convection Enhanced Delivery ◽  
Brain White Matter ◽  
Significant Difference ◽  
The Brain

Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue, as in Convection-Enhanced Delivery procedures. The proposed research analyzes the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of electron microscopy images. We cut the two volumes with 20 equally spaced planes distributed along two perpendicular directions, and, on each plane, we computed the corresponding permeability vector. Then, we considered that the WM structure is mainly composed of elongated and parallel axons, and, using a principal component analysis, we defined two principal directions, parallel and perpendicular, with respect to the axons’ main direction. The latter were used to define a reference frame onto which the permeability vectors were projected to finally obtain the permeability along the parallel and perpendicular directions. The results show a statistically significant difference between parallel and perpendicular permeability, with a ratio of about two in both the WM structures analyzed, thus demonstrating their anisotropic behavior. Moreover, we find a significant difference between permeability in corpus callosum and fornix, which suggests that the WM heterogeneity should also be considered when modeling drug transport in the brain. Our findings, which demonstrate and quantify the anisotropic and heterogeneous character of the WM, represent a fundamental contribution not only for drug-delivery modeling, but also for shedding light on the interstitial transport mechanisms in the extracellular space.

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