Selective Vulnerability of the Brain in Hypoxaemia

1964 ◽  
Vol 139 (4) ◽  
pp. 399
Author(s):  
Robert G. Grenell
Keyword(s):  
Selective Vulnerability ◽  
The Brain

scholarly journals Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angela M. Crist ◽  
Kelly M. Hinkle ◽  
Xue Wang ◽  
Christina M. Moloney ◽  
Billie J. Matchett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Digital Pathology ◽  
Selective Vulnerability ◽  
Brain Regions ◽  
Biochemical Analyses ◽  
The Brain ◽  
Relevant Gene ◽  
Tau Expression

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

Selective Vulnerability

2017 ◽  
Author(s):  
Robert Laureno
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Brain Structures ◽  
Selective Vulnerability ◽  
Brain Regions ◽  
Degenerative Diseases ◽  
Selective System ◽  
Hereditary Disorders ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Different Parts

This chapter on “Selective Vulnerability” examines the selective vulnerability of different parts of the brain to particular diseases. In one disease, certain areas of brain are particularly vulnerable. In other diseases, different parts of the brain are more susceptible. The concept of selective vulnerability was originally applied to toxic/metabolic and hereditary disorders, but it is also useful in thinking about other neuropathologic processes including neoplastic, infectious, demyelinative, vascular, and traumatic diseases. Diseases can selectively affect brain systems, brain structures, or brain regions. Selective system involvement is clear in degenerative diseases such as amyotrophic lateral sclerosis; selective structure involvement occurs in carbon monoxide’s effect on the globus pallidus; selective region involvement is found in myelinolysis.

Cerebral Palsy

2017 ◽  
Author(s):  
Joan M. Jasien ◽  
Bruce K. Shapiro ◽  
Alexander H. Hoon
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Human Brain ◽  
Selective Vulnerability ◽  
Postnatal Life ◽  
Organizational Changes ◽  
Immature Brain ◽  
The Brain ◽  
Compensatory Plasticity ◽  
Over Time

Cerebral palsy (CP) describes a group of disorders of movement/posture causing activity limitation that are attributed to nonprogressive disturbances in the immature brain that can change over time. The immature human brain undergoes organizational changes during intrauterine and postnatal life creating potential temporal periods of selective vulnerability to damage. Understanding the compensatory plasticity process after the brain injury may provide new insights into the pathogenesis of CP.

scholarly journals The Norepinephrine Metabolite DOPEGAL Confers Locus Coeruleus Tau Vulnerability and Propagation via Asparagine Endopeptidase

2019 ◽  
Author(s):  
Seong Su Kang ◽  
Xia Liu ◽  
Eun Hee Ahn ◽  
Jie Xiang ◽  
Fredric P. Manfredsson ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Locus Coeruleus ◽  
Selective Vulnerability ◽  
Monoamine Oxidase A ◽  
Noradrenergic Neurons ◽  
Tau Pathology ◽  
Intact Cells ◽  
Tau Aggregation ◽  
The Brain

AbstractAberrant Tau inclusions in the locus coeruleus (LC) are the earliest detectable Alzheimer’s disease (AD)-like neuropathology in the human brain; however, why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in disease and whether the LC might seed the stereotypical spread of Tau pathology to the rest of the brain remain unclear. Here we show that 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), which is produced exclusively in noradrenergic neurons by monoamine oxidase A (MAO-A) metabolism of norepinephrine (NE), activates asparagine endopeptidase (AEP) that cleaves Tau at residue N368 into aggregation- and propagation-prone forms, thereby leading to LC degeneration and the spread of Tau pathology. DOPEGAL triggers AEP-cleaved Tau aggregationin vitroand in intact cells, resulting in LC neurotoxicity and propagation of pathology to the forebrain. Thus, our findings reveal a novel molecular mechanism underlying the selective vulnerability of LC neurons in AD.

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