Beyond axonal transection: Hippocampal damage in multiple sclerosis

2011 ◽  
Vol 69 (3) ◽  
pp. 433-436 ◽  
Author(s):  
Orhan Aktas ◽  
Hans-Peter Hartung
Keyword(s):  
Multiple Sclerosis ◽  
Hippocampal Damage ◽  
Axonal Transection

scholarly journals Cognitive Impairment in Multiple Sclerosis

Folia Medica ◽  
2016 ◽  
Vol 58 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Anastasiya G. Trenova ◽  
Georgi S. Slavov ◽  
Maria G. Manova ◽  
Jana B. Aksentieva ◽  
Lyuba D. Miteva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Disorders ◽  
Social Burden ◽  
Immune Mediated ◽  
The Social ◽  
The Central Nervous System ◽  
Axonal Transection ◽  
The Relationship

Abstract Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients’ quality of life, independently from the course and phase of the disease. The relationship between pathological brain findings and cognitive impairment is a subject of intensive research. Summarizing recent data about prevalence, clinical specificity and treatment of cognitive disorders in MS, this review aims to motivate the necessity of early diagnosis and complex therapeutic approach to these disturbances in order to reduce the social burden of the disease.

Alterations in neuronal gene expression profiles in response to experimental demyelination and axonal transection

2010 ◽  
Vol 16 (3) ◽  
pp. 303-316 ◽  
Author(s):  
G. Lovas ◽  
JA Nielsen ◽  
KR Johnson ◽  
LD Hudson
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neurological Deficits ◽  
Activating Transcription Factor 3 ◽  
Post Intervention ◽  
Neuronal Gene ◽  
Activating Transcription Factor ◽  
Axonal Transection

The main pathological features of multiple sclerosis, demyelination and axonal transection, are considered to cause reversible and irreversible neurological deficits, respectively. This study aimed to separately analyze the effects of these pathological hallmarks on neuronal gene expression in experimental paradigms. The pontocerebellar pathway was targeted with either lysolecithin-induced chemical demyelination or a complete pathway transection (axonal transection) in rats. Transcriptional changes in the pontocerebellar neurons were investigated with microarrays at days 4, 10 and 37 post-intervention, which was confirmed by immunohistochemistry on protein level. A common as well as unique set of injury-response genes was identified. The increased expression of activating transcription factor 3 (Atf3) and thyrotropin-releasing hormone (Trh) in both injury paradigms was validated by immunohistochemistry. The expression of Atf3 in a patient with Marburg’s variant of multiple sclerosis was also detected, also confirming the activation of the Atf3 pathway in a human disease sample. It was concluded that this experimental approach may be useful for the identification of pathways that could be targeted for remyelinative or neuroprotective drug development.

scholarly journals Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis

2016 ◽  
Vol 23 (9) ◽  
pp. 1214-1224 ◽  
Author(s):  
Vincent Planche ◽  
Aurélie Ruet ◽  
Pierrick Coupé ◽  
Delphine Lamargue-Hamel ◽  
Mathilde Deloire ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Verbal Memory ◽  
Predictive Value ◽  
Memory Impairment ◽  
Diffusion Tensor ◽  
Memory Performance ◽  
Mean Diffusivity ◽  
Clinically Isolated Syndrome ◽  
Hippocampal Damage ◽  
Lesion Load

Objective: We investigated whether diffusion tensor imaging (DTI) could reveal early hippocampal damage and clinically relevant correlates of memory impairment in persons with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: A total of 37 persons with CIS, 32 with MS and 36 controls prospectively included from 2011 to 2014 were tested for cognitive performances and scanned with 3T-magnetic resonance imaging (MRI) to assess volumetric and DTI changes within the hippocampus, whole brain volume and T2-lesion load. Results: While there was no hippocampal atrophy in the CIS group, hippocampal fractional anisotropy (FA) was significantly decreased compared to controls. Decrease in hippocampal FA together with increased mean diffusivity (MD) was even more prominent in MS patients. In CIS, hippocampal MD was correlated with episodic verbal memory performance ( r = −0.57, p = 0.0002 and odds ratio (OR) = 0.058, 95% confidence interval (CI) = 0.0057–0.59, p = 0.016 adjusted for age, gender, depression and T2-lesion load), but not with cognitive tasks unrelated to hippocampal functions. Hippocampal MD was the only variable discriminating memory-impaired from memory-preserved persons with CIS (area under the curve (AUC) = 0.77, sensitivity = 90.0%, specificity = 70.3%, positive predictive value (PPV) = 52.9%, negative predictive value (NPV) = 95.0%). Conclusion: DTI alterations within the hippocampus might reflect early neurodegenerative processes that are correlated with episodic memory performance, discriminating persons with CIS according to their memory status.

scholarly journals The role of hippocampal theta oscillations in working memory impairment in multiple sclerosis

2020 ◽  
Author(s):  
Lars Costers ◽  
Jeroen Van Schependom ◽  
Jorne Laton ◽  
Johan Baijot ◽  
Martin Sjøgård ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Working Memory ◽  
Healthy Subjects ◽  
Neuronal Damage ◽  
Hippocampal Damage ◽  
Theta Power ◽  
Power Increase ◽  
Neurophysiological Mechanisms ◽  
The Right ◽  
Hippocampal Theta

AbstractWorking memory (WM) problems are frequent in persons with multiple sclerosis (MS). Even though hippocampal damage has been repeatedly shown to play an important role, the underlying neurophysiological mechanisms remain unclear. This study aimed to investigate the neurophysiological underpinnings of WM impairment in MS using magnetoencephalography (MEG) data from a verbal n-back task. We analysed MEG recordings of 79 MS patients and 38 healthy subjects through event-related fields (ERFs) and theta (4-8 Hz) and alpha (8-13 Hz) oscillatory processes. Data was source reconstructed and parcellated based on previous findings in the healthy subject sample. MS patients showed a smaller maximum theta power increase in the right hippocampus between 0 and 400 ms than healthy subjects (p = 0.014). This theta power increase value correlated strongly and negatively with reaction time on the task in MS (r = −0.32, p = 0.029). Evidence was provided that this relationship could not be explained by a confounding relationship with MS-related neuronal damage. This study provides the first neurophysiological evidence of the influence of hippocampal dysfunction on WM performance in MS.

scholarly journals Remyelination Trials

2021 ◽  
Vol 8 (6) ◽  
pp. e1066
Author(s):  
Alexandr Klistorner ◽  
Michael Barnett
Keyword(s):  
Multiple Sclerosis ◽  
Pharmaceutical Industry ◽  
Tissue Damage ◽  
Axonal Degeneration ◽  
Neuroprotective Strategy ◽  
Axonal Transection

Neuroaxonal loss is believed to underpin the progressive disability that characterizes multiple sclerosis (MS). While focal inflammatory demyelination is a principal cause of acute axonal transection and subsequent axonal degeneration, the gradual attrition of permanently demyelinated axons may also contribute to tissue damage, particularly in the progressive phase of the disease. Therefore, remyelination is considered a putative neuroprotective strategy. In this article, we review the potential pitfalls of remyelination trials, provide a framework for their appropriate design and temper the expectations, at times unrealistic, of researchers, regulators and the pharmaceutical industry.

Axonal Transection in the Lesions of Multiple Sclerosis

1998 ◽  
Vol 338 (5) ◽  
pp. 278-285 ◽  
Author(s):  
Bruce D. Trapp ◽  
John Peterson ◽  
Richard M. Ransohoff ◽  
Richard Rudick ◽  
Sverre Mörk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Transection

Microglia-derived macrophages in early multiple sclerosis plaques

1996 ◽  
Vol 22 (3) ◽  
pp. 207-215 ◽  
Author(s):  
H. Li ◽  
M. L. Cuzner ◽  
J. Newcombe
Keyword(s):  
Multiple Sclerosis
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