Neurite Outgrowth Inhibitor (NogoA) Is Upregulated in White Matter Lesions of Complex Cortical Malformations

2021 ◽  
Vol 80 (3) ◽  
pp. 274-282
Author(s):  
Theresa Scholl ◽  
Victoria-Elisabeth Gruber ◽  
Sharon Samueli ◽  
Reinhard Lehner ◽  
Gregor Kasprian ◽  
...  
Keyword(s):  
White Matter ◽  
Neurite Outgrowth ◽  
Focal Cortical Dysplasia ◽  
Mammalian Target Of Rapamycin ◽  
White Matter Lesions ◽  
Cortical Malformations ◽  
Developmental Impairment ◽  
Cortical Tubers ◽  
Drug Resistant Epilepsy

Abstract Complex cortical malformations (CCMs), such as hemimegalencephaly and polymicrogyria, are associated with drug-resistant epilepsy and developmental impairment. They share certain neuropathological characteristics including mammalian target of rapamycin (mTOR) activation and an atypical number of white matter neurons. To get a better understanding of the pathobiology of the lesion architecture, we investigated the role of neurite outgrowth inhibitor A (NogoA), a known regulator of neuronal migration. Epilepsy surgery specimens from 16 CCM patients were analyzed and compared with sections of focal cortical dysplasia IIB (FCD IIB, n = 22), tuberous sclerosis complex (TSC, n = 8) as well as healthy controls (n = 15). Immunohistochemistry was used to characterize NogoA, myelination, and mTOR signaling. Digital slides were evaluated automatically with ImageJ. NogoA staining showed a significantly higher expression within the white matter of CCM and FCD IIB, whereas cortical tubers presented levels similar to controls. Further analysis of possible associations of NogoA with other factors revealed a positive correlation with mTOR and seizure frequency. To identify the main expressing NogoA cell type, double staining revealed dysmorphic neuronal white matter cells. Increased NogoA expression is associated with profound inhibition of neuritic sprouting and therefore contributes to a decrease in neuronal network complexity in CCM patients.

scholarly journals Implication of Contactins in Demyelinating Pathologies

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Ilias Kalafatakis ◽  
Maria Savvaki ◽  
Theodora Velona ◽  
Domna Karagogeos
Keyword(s):  
Nervous System ◽  
White Matter ◽  
Cell Adhesion Molecules ◽  
White Matter Lesions ◽  
Myelinated Axon ◽  
Immunoglobulin Superfamily ◽  
Proper Function ◽  
Myelinated Axons ◽  
And Function

Demyelinating pathologies comprise of a variety of conditions where either central or peripheral myelin is attacked, resulting in white matter lesions and neurodegeneration. Myelinated axons are organized into molecularly distinct domains, and this segregation is crucial for their proper function. These defined domains are differentially affected at the different stages of demyelination as well as at the lesion and perilesion sites. Among the main players in myelinated axon organization are proteins of the contactin (CNTN) group of the immunoglobulin superfamily (IgSF) of cell adhesion molecules, namely Contactin-1 and Contactin-2 (CNTN1, CNTN2). The two contactins perform their functions through intermolecular interactions, which are crucial for myelinated axon integrity and functionality. In this review, we focus on the implication of these two molecules as well as their interactors in demyelinating pathologies in humans. At first, we describe the organization and function of myelinated axons in the central (CNS) and the peripheral (PNS) nervous system, further analyzing the role of CNTN1 and CNTN2 as well as their interactors in myelination. In the last section, studies showing the correlation of the two contactins with demyelinating pathologies are reviewed, highlighting the importance of these recognition molecules in shaping the function of the nervous system in multiple ways.

Role of White Matter Lesions in Cognitive Impairment of Vascular Origin

1999 ◽  
Vol 13 (Supplement) ◽  
pp. S49-54 ◽  
Author(s):  
Leonardo Pantoni ◽  
Didier Leys ◽  
Franz Fazekas ◽  
Will T. Longstreth ◽  
Domenico Inzitari ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
White Matter Lesions ◽  
Vascular Origin

scholarly journals Modeling the Encephalopathy of Prematurity in Animals: The Important Role of Translational Research

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Hannah C. Kinney ◽  
Joseph J. Volpe
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Animal Models ◽  
Translational Research ◽  
Developmental Trajectories ◽  
Axonal Injury ◽  
White Matter Lesions ◽  
Human Condition ◽  
Cerebral White Matter

Translational research in preterm brain injury depends upon the delineation of the human neuropathology in order that animal models faithfully reiterate it, thereby ensuring direct relevance to the human condition. The major substrate of human preterm brain injury is the encephalopathy of prematurity that is characterized by gray and white matter lesions reflecting combined acquired insults, altered developmental trajectories, and reparative phenomena. Here we highlight the key features of human preterm brain development and the encephalopathy of prematurity that are critical for modeling in animals. The complete mimicry of the complex human neuropathology is difficult in animal models. Many models focus upon mechanisms related to a specific feature, for example, loss of premyelinating oligodendrocytes in the cerebral white matter. Nevertheless, animal models that simultaneously address oligodendrocyte, neuronal, and axonal injury carry the potential to decipher shared mechanisms and synergistic treatments to ameliorate the global consequences of the encephalopathy of prematurity.

White matter lesions: role of spin density in MR imaging.

Radiology ◽  
1989 ◽  
Vol 170 (3) ◽  
pp. 863-868 ◽  
Author(s):  
J R Geis ◽  
R E Hendrick ◽  
S Lee ◽  
K A Davis ◽  
D Thickman
Keyword(s):  
White Matter ◽  
Mr Imaging ◽  
Spin Density ◽  
White Matter Lesions

Neuroimaging in Migraine—Recent Advances and Perspectives for the Future

US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 82
Author(s):  
Brian K Day ◽  
David W Dodick ◽  
Todd J Schwedt ◽  
◽  
◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Lesions ◽  
Medical Decision ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual ◽  
Sites Of Action ◽  
Functional Connectivity Mri ◽  
Neuroimaging Techniques

Migraine is a very common disorder that imposes substantial individual and societal costs. A better understanding of migraine mechanisms may lead to the development of new therapies and thus improve the management of migraine patients. Magnetic resonance imaging (MRI) techniques and positron emission tomography (PET) have revolutionized our understanding of migraine pathophysiology as a primary central nervous system (CNS) disorder, advanced the search for a central migraine generator, clarified the role of cortical spreading depression (CSD) and central sensitization in the pathogenesis of migraine, and revealed some potential sites of action of migraine medications. Structural imaging has shed light on relationships between migraine and stroke, white matter lesions, iron deposition, microstructural brain damage, and other gray and white matter aberrations. Emerging neuroimaging techniques, such as arterial spin labeling (ASL) and functional connectivity MRI (fcMRI), are beginning to provide further evidence of functional brain alterations in migraine patients. Ultimately, it is hoped that advanced neuroimaging will benefit the individual migraine patient by enhancing our diagnostic abilities, allowing for development of better treatments and serving as an important tool in medical decision-making.

scholarly journals Cerebral white matter lesions and perceived cognitive dysfunction: the role of pregnancy

2014 ◽  
Vol 211 (3) ◽  
pp. 257.e1-257.e5 ◽  
Author(s):  
Ineke R. Postma ◽  
Jan Cees de Groot ◽  
Annet M. Aukes ◽  
Jan G. Aarnoudse ◽  
Gerda G. Zeeman
Keyword(s):  
White Matter ◽  
Cognitive Dysfunction ◽  
White Matter Lesions ◽  
Cerebral White Matter ◽  
Cerebral White Matter Lesions

HLA-DPB1*0501 is not uniquely associated with opticospinal multiple sclerosis in Japanese patients. Important role of DPB1*0301

2006 ◽  
Vol 12 (1) ◽  
pp. 19-23 ◽  
Author(s):  
T Fukazawa ◽  
S Kikuchi ◽  
R Miyagishi ◽  
Y Miyazaki ◽  
I Yabe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Strong Association ◽  
White Matter Lesions ◽  
Normal Subjects ◽  
Japanese Patients ◽  
Periventricular White Matter ◽  
Periventricular Lesions ◽  
Periventricular White Matter Lesions

Apart from its unique lesion distribution pattern, the opticospinal form of multiple sclerosis (OSMS) is distinct among Japanese patients who satisfy the diagnostic criteria of MS. OSMS has been suggested to be strongly associated with HLA-DPB1*0501 in Japanese. However, association of DPB1*0301 with non-OSMS and lack of DPB1*0301 in OSMS were also reported. To verify the role of DPB1*0501 and DPB1*0301 in Japanese MS patients we determined the frequencies of these alleles in 26 patients with OSMS, 167 with non-OSMS and 156 normal subjects, who were all residents of Hokkaido, the northernmost island of Japan. All (100%) OSMS were negative for DPB1*0301 while 32 (19%) of the non-OSMS were positive for the allele. In DPB1*0301-negatives, the frequencies of DPB1*0501 in OSMS (85%) and non-OSMS (82%) were similar, but both were higher than in the controls (66%). In DPB1*0301-positives, the frequency of DPB1*0501 was low but similar in non-OSMS (12/32; 38%) and controls (6/14; 43%). Periventricular white matter lesions (PVL) were noted in 31 of 32 (97%) DPB1*0301-positive non-OSMS patients but in only 22 out of 135 (16%) DPB1*0301-negative non-OSMS patients and two out of 26 (8%) OSMS patients. Our findings indicate that DPB1*0501 plays an important role in the development of MS in general, but not in OSMS. The strong association of DPB1*0501 with OSMS may be due to the over-representation of the DPB1*0301 allele among individuals in the non-OSMS group. In addition, DPB1*0301 might be relevant to the development of periventricular lesions in Japanese patients with MS.

scholarly journals Role of Tissue-Derived Plasminogen Activator (t-PA) in an Excitotoxic Mouse Model of Neonatal White Matter Lesions

2004 ◽  
Vol 63 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Olivier Hennebert ◽  
Stéphane Marret ◽  
Peter Carmeliet ◽  
Pierre Gressens ◽  
Annie Laquerrière ◽  
...  
Keyword(s):  
White Matter ◽  
Mouse Model ◽  
Plasminogen Activator ◽  
White Matter Lesions
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