Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Uzdensky, Anatoly B.; Demyanenko, Svetlana; Федоренко, Г. М.; Lapteva, T.O.; Fedorenko, A.G.

doi:10.1007/s12035-016-9964-5

Cited by 45 publications

(27 citation statements)

References 68 publications

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“…Such bead-like deformations have been reported to occur as axonal “blebbing” in cell culture experiments as soon as 15 min after the insult and are shown to lead to extensive axonal degeneration ( Castillo and Babson, 1998 ). Accordingly, swelling of neurites was observed in the setting of focal cerebral ischemia ( Uzdensky et al, 2016 ). Of note, in the present study, these bulb-like structures often appeared to be disconnected from each other as exemplified by NF-L labeling ( Figures 8D,F ).…”

Section: Discussionmentioning

confidence: 99%

Impaired Neurofilament Integrity and Neuronal Morphology in Different Models of Focal Cerebral Ischemia and Human Stroke Tissue

Mages

Aleithe

Altmann

et al. 2018

Front. Cell. Neurosci.

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As part of the neuronal cytoskeleton, neurofilaments are involved in maintaining cellular integrity. In the setting of ischemic stroke, the affection of the neurofilament network is considered to mediate the transition towards long-lasting tissue damage. Although peripheral levels of distinct neurofilament subunits are shown to correlate with the clinically observed severity of cerebral ischemia, neurofilaments have so far not been considered for neuroprotective approaches. Therefore, the present study systematically addresses ischemia-induced alterations of the neurofilament light (NF-L), medium (NF-M), and heavy (NF-H) subunits as well as of α-internexin (INA). For this purpose, we applied a multi-parametric approach including immunofluorescence labeling, western blotting, qRT-PCR and electron microscopy. Analyses comprised ischemia-affected tissue from three stroke models of middle cerebral artery occlusion (MCAO), including approaches of filament-based MCAO in mice, thromboembolic MCAO in rats, and electrosurgical MCAO in sheep, as well as human autoptic stroke tissue. As indicated by altered immunosignals, impairment of neurofilament subunits was consistently observed throughout the applied stroke models and in human tissue. Thereby, altered NF-L immunoreactivity was also found to reach penumbral areas, while protein analysis revealed consistent reductions for NF-L and INA in the ischemia-affected neocortex in mice. At the mRNA level, the ischemic neocortex and striatum exhibited reduced expressions of NF-L- and NF-H-associated genes, whereas an upregulation for Ina appeared in the striatum. Further, multiple fluorescence labeling of neurofilament proteins revealed spheroid and bead-like structural alterations in human and rodent tissue, correlating with a cellular edema and lost cytoskeletal order at the ultrastructural level. Thus, the consistent ischemia-induced affection of neurofilament subunits in animals and human tissue, as well as the involvement of potentially salvageable tissue qualify neurofilaments as promising targets for neuroprotective strategies. During ischemia formation, such approaches may focus on the maintenance of neurofilament integrity, and appear applicable as co-treatment to modern recanalizing strategies.

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Section: Discussionmentioning

confidence: 99%

Impaired Neurofilament Integrity and Neuronal Morphology in Different Models of Focal Cerebral Ischemia and Human Stroke Tissue

Mages

Aleithe

Altmann

et al. 2018

Front. Cell. Neurosci.

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“…Some studies have suggested a loss or inefficiency in DA nerve terminals, with animals with more severe strokes having 30%, and moderately affected animals having 66%, of the number of DA nerve terminals of the contralateral hemisphere (Weinberger et al, 1983 ). In a rat photothrombosis model employing less intensive but longer duration irradiation to simulate a penumbra zone, levels of MAO-B were increased ~3-fold in the penumbra as compared to contralateral tissue at 4 h poststroke and ~2-fold at 24 h poststroke (Uzdensky et al, 2017 ). DOPA decarboxylase and TH were down regulated.…”

Section: Effect Of Stroke On Functioning Of the Dopaminergic Systemmentioning

confidence: 99%

“…DOPA decarboxylase and TH were down regulated. Additionally, DAT levels were lower than the contralateral side (Uzdensky et al, 2017 ). These regulatory changes in the penumbra suggest lower DA levels are available after the immediate stroke period.…”

Section: Effect Of Stroke On Functioning Of the Dopaminergic Systemmentioning

confidence: 99%

The Intersection of Central Dopamine System and Stroke: Potential Avenues Aiming at Enhancement of Motor Recovery

Gower

Tiberi

2018

Front. Synaptic Neurosci.

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Dopamine, a major neurotransmitter, plays a role in a wide range of brain sensorimotor functions. Parkinson's disease and schizophrenia are two major human neuropsychiatric disorders typically associated with dysfunctional dopamine activity levels, which can be alleviated through the druggability of the dopaminergic systems. Meanwhile, several studies suggest that optimal brain dopamine activity levels are also significantly impacted in other serious neurological conditions, notably stroke, but this has yet to be fully appreciated at both basic and clinical research levels. This is of utmost importance as there is a need for better treatments to improve recovery from stroke. Here, we discuss the state of knowledge regarding the modulation of dopaminergic systems following stroke, and the use of dopamine boosting therapies in animal stroke models to improve stroke recovery. Indeed, studies in animals and humans show stroke leads to changes in dopamine functioning. Moreover, evidence from animal stroke models suggests stimulation of dopamine receptors may be a promising therapeutic approach for enhancing motor recovery from stroke. With respect to the latter, we discuss the evidence for several possible receptor-linked mechanisms by which improved motor recovery may be mediated. One avenue of particular promise is the subtype-selective stimulation of dopamine receptors in conjunction with physical therapy. However, results from clinical trials so far have been more mixed due to a number of potential reasons including, targeting of the wrong patient populations and use of drugs which modulate a wide array of receptors. Notwithstanding these issues, it is hoped that future research endeavors will assist in the development of more refined dopaminergic therapeutic approaches to enhance stroke recovery.

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“…The resulting imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombogenesis could contribute to stroke pathophysiology during SARS-CoV-2 infection. 50 Our results indicated a broad presence of ACE2 and TMPRSS2 in CNS tissues that are closely associated with stroke, including the cerebellum, 51 corpus callosum, 52 hippocampus, 53 frontal lobe, 54 cerebral cortex, 55 and others. Therefore, the tissue tropism of SARS-CoV-2 for ACE2 (or TMPRSS2) and the inflammatory cytokine storm caused by COVID-19 might be an underlying mechanism for stroke.…”

Section: Discussionmentioning

confidence: 72%

<p>Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19</p>

Ren¹,

Wang²,

Chen³

et al. 2020

IDR

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Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Cited by 45 publications

References 68 publications

Impaired Neurofilament Integrity and Neuronal Morphology in Different Models of Focal Cerebral Ischemia and Human Stroke Tissue

Impaired Neurofilament Integrity and Neuronal Morphology in Different Models of Focal Cerebral Ischemia and Human Stroke Tissue

The Intersection of Central Dopamine System and Stroke: Potential Avenues Aiming at Enhancement of Motor Recovery

<p>Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19</p>

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