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The spatial cerebral damage caused by larger infarct and β‐amyloid toxicity is driven by the anatomical/functional connectivity
Author(s) -
Amtul Zareen,
Frías Carmen,
Randhawa Jasmine,
Hill David J.,
Arany Edith J.
Publication year - 2020
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.24738
Subject(s) - white matter , internal capsule , neuroscience , corpus callosum , external capsule , medicine , toxicity , lesion , brain damage , globus pallidus , striatum , neuroinflammation , ischemia , pathology , psychology , central nervous system , disease , basal ganglia , magnetic resonance imaging , radiology , dopamine
Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce. It remains to be determined if the co‐morbid concurrence of large infarct and β‐amyloid (Aβ) toxicity can precipitate the early development of dementia. Here, we described a dose‐dependent effect of a unilateral striatal injection of vasoconstrictive endothelin‐1 (ET‐1) along with Aβ toxicity on CNS pathogenesis; driven by the anatomical and functional networks within a brain circuit. After 21 days of treatment, a high dose (60 pmol) of ET‐1 (E60) alone caused the greatest increase in neuroinflammation, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion such as white matter (subcortical white matter, corpus callosum, internal capsule, anterior commissure), gray matter (globus pallidus, thalamus), and cortices (cingulate, motor, somatosensory, entorhinal). The combined E60 + Aβ treatment also extended perturbation in the contralateral hemisphere of these rats, such as increased deposition of amyloid precursor protein fragments associated with the appearance of degenerating cells and the leakage of laminin from the basement membrane across a compromised blood–brain barrier. However, the cerebral damage induced by the 6 pmol ET‐1 (E6), Aβ and E6 + Aβ rats was not detrimental enough to injure the complete network. The appreciation of the causal interactions among distinct anatomical units in the brain after ischemia and Aβ toxicity will help in the design of effective and alternative therapeutics that may disassociate the synergistic or additive association between the infarcts and Aβ toxicity.