Alterations of the blood-spinal cord barrier in sporadic amyotrophic lateral sclerosis

2015 ◽  
Vol 35 (6) ◽  
pp. 518-528 ◽  
Author(s):  
Shoichi Sasaki
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Blood Spinal Cord Barrier ◽  
Lateral Sclerosis

Activation of Signal Transducer and Activator of Transcription-3 in the Spinal Cord of Sporadic Amyotrophic Lateral Sclerosis Patients

2009 ◽  
Vol 6 (3) ◽  
pp. 118-126 ◽  
Author(s):  
Noriyuki Shibata ◽  
Akiyoshi Kakita ◽  
Hitoshi Takahashi ◽  
Yuetsu Ihara ◽  
Keigo Nobukuni ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Signal Transducer ◽  
Transcription 3 ◽  
Lateral Sclerosis

scholarly journals Altered Blood-Brain Barrier and Blood-Spinal Cord Barrier Dynamics in Amyotrophic Lateral Sclerosis: Impact on Medication Efficacy and Safety

2021 ◽  
Author(s):  
Yijun Pan ◽  
Joseph Nicolazzo
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Large Body ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Spinal Cord Barrier ◽  
The Brain ◽  
Lateral Sclerosis

The access of drugs into the central nervous system (CNS) is regulated by the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). A large body of evidence supports perturbation of these barriers in neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Modifications to the BBB and BSCB are also reported in amyotrophic lateral sclerosis (ALS), albeit these modifications have received less attention relative to those in other neurodegenerative diseases. Such alterations to the BBB and BSCB have the potential to impact on CNS exposure of drugs in ALS, modulating the effectiveness of drugs intended to reach the brain and the toxicity of drugs that are not intended to reach the brain. Given the clinical importance of these phenomena, this review will summarise reported modifications to the BBB and BSCB in ALS, discuss their impact on CNS drug exposure and suggest further research directions so as to optimise medicine use in people with ALS.

scholarly journals TDP-43 Vasculopathy in the Spinal Cord in Sporadic Amyotrophic Lateral Sclerosis (sALS) and Frontal Cortex in sALS/FTLD-TDP

2021 ◽  
Vol 80 (3) ◽  
pp. 229-239
Author(s):  
Isidro Ferrer ◽  
Pol Andrés-Benito ◽  
Margarita Carmona ◽  
Abdelilah Assialioui ◽  
Mónica Povedano
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Frontal Cortex ◽  
Blood Vessels ◽  
External Surface ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Double Labeling ◽  
Cortex Area ◽  
Altered Blood ◽  
Lateral Sclerosis

Abstract Sporadic amyotrophic lateral sclerosis (sALS) and FTLD-TDP are neurodegenerative diseases within the spectrum of TDP-43 proteinopathies. Since abnormal blood vessels and altered blood-brain barrier have been described in sALS, we wanted to know whether TDP-43 pathology also occurs in blood vessels in sALS/FTLD-TDP. TDP-43 deposits were identified in association with small blood vessels of the spinal cord in 7 of 14 cases of sALS and in small blood vessels of frontal cortex area 8 in 6 of 11 FTLD-TDP and sALS cases, one of them carrying a GRN mutation. This was achieved using single and double-labeling immunohistochemistry, and double-labeling immunofluorescence and confocal microscopy. In the sALS spinal cord, P-TDP43 Ser403-404 deposits were elongated and parallel to the lumen, whereas others were granular, seldom forming clusters. In the frontal cortex, the inclusions were granular, or elongated and parallel to the lumen, or forming small globules within or in the external surface of the blood vessel wall. Other deposits were localized in the perivascular space. The present findings are in line with previous observations of TDP-43 vasculopathy in a subset of FTLD-TDP cases and identify this pathology in the spinal cord and frontal cortex in a subset of cases within the sALS/FTLD-TDP spectrum.

scholarly journals Pathophysiological Correlation between Cigarette Smoking and Amyotrophic Lateral Sclerosis

NeuroSci ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 120-134
Author(s):  
Spiro Menounos ◽  
Philip M. Hansbro ◽  
Ashish D. Diwan ◽  
Abhirup Das
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Risk Factor ◽  
Disease Process ◽  
Future Research ◽  
Environmental Risk Factor ◽  
Sporadic Als ◽  
Blood Spinal Cord Barrier ◽  
Lateral Sclerosis

Cigarette smoke (CS) has been consistently demonstrated to be an environmental risk factor for amyotrophic lateral sclerosis (ALS), although the molecular pathogenic mechanisms involved are yet to be elucidated. Here, we propose different mechanisms by which CS exposure can cause sporadic ALS pathogenesis. Oxidative stress and neuroinflammation are widely implicated in ALS pathogenesis, with blood–spinal cord barrier disruption also recognised to be involved in the disease process. In addition, immunometabolic, epigenetic and microbiome alterations have been implicated in ALS recently. Identification of the underlying pathophysiological mechanisms that underpin CS-associated ALS will drive future research to be conducted into new targets for treatment.

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