Cognition, Statins, and Cholesterol in Elderly Ischemic Stroke Patients: A Neurologist’s Perspective

Simion

2021

IJMS

Self Cite

236

Its increasing incidence has led stroke to be the second leading cause of death worldwide. Despite significant advances in recanalization strategies, patients are still at risk for ischemia/reperfusion injuries in this pathophysiology, in which neuroinflammation is significantly involved. Research has shown that in the acute phase, neuroinflammatory cascades lead to apoptosis, disruption of the blood–brain barrier, cerebral edema, and hemorrhagic transformation, while in later stages, these pathways support tissue repair and functional recovery. The present review discusses the various cell types and the mechanisms through which neuroinflammation contributes to parenchymal injury and tissue repair, as well as therapeutic attempts made in vitro, in animal experiments, and in clinical trials which target neuroinflammation, highlighting future therapeutic perspectives.

Section: Therapeutic Approaches Focusing On Modulation Of Neuroinflammationmentioning

confidence: 99%

Neuroinflammation in Cerebral Ischemia and Ischemia/Reperfusion Injuries: From Pathophysiology to Therapeutic Strategies

Simion

2021

IJMS

Self Cite

236

“…Oxidative stress is an imbalance between the rate of generation of ROS and the biological system's ability to clear these highly reactive molecules [14]. The cerebral tissue is particularly sensitive to oxidative stress due to a series of features, such as [15][16][17][18]:…”

Section: Oxidative Stress In the Pathophysiology Of Ischemia/reperfus...mentioning

confidence: 99%

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

Ardelean

2022

Biomedicines

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Recanalization therapy is increasingly used in the treatment of acute ischemic stroke. However, in about one third of these patients, recanalization is followed by ischemia/reperfusion injuries, and clinically to worsening of the neurological status. Much research has focused on unraveling the involved mechanisms in order to prevent or efficiently treat these injuries. What we know so far is that oxidative stress and mitochondrial dysfunction are significantly involved in the pathogenesis of ischemia/reperfusion injury. However, despite promising results obtained in experimental research, clinical studies trying to interfere with the oxidative pathways have mostly failed. The current article discusses the main mechanisms leading to ischemia/reperfusion injuries, such as mitochondrial dysfunction, excitotoxicity, and oxidative stress, and reviews the clinical trials with antioxidant molecules highlighting recent developments and future strategies.

“…In addition, astrocytes play a key role in cholesterol synthesis in the adult brain [ 301 ]. HD associates dysregulated cholesterol metabolism, with lower 24-hydroxy-cholesterol plasmatic levels reported both in HD patients as well as in rodent models [ 302 ], both through altered gene expression and at the transcriptional level.…”

Section: Mechanisms Of Neurodegeneration In Huntington’s Diseasementioning

confidence: 99%

Molecular Pathophysiological Mechanisms in Huntington’s Disease

2022

Biomedicines

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Huntington’s disease is an inherited neurodegenerative disease described 150 years ago by George Huntington. The genetic defect was identified in 1993 to be an expanded CAG repeat on exon 1 of the huntingtin gene located on chromosome 4. In the following almost 30 years, a considerable amount of research, using mainly animal models or in vitro experiments, has tried to unravel the complex molecular cascades through which the transcription of the mutant protein leads to neuronal loss, especially in the medium spiny neurons of the striatum, and identified excitotoxicity, transcriptional dysregulation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, altered axonal trafficking and reduced availability of trophic factors to be crucial contributors. This review discusses the pathogenic cascades described in the literature through which mutant huntingtin leads to neuronal demise. However, due to the ubiquitous presence of huntingtin, astrocytes are also dysfunctional, and neuroinflammation may additionally contribute to Huntington’s disease pathology. The quest for therapies to delay the onset and reduce the rate of Huntington’s disease progression is ongoing, but is based on findings from basic research.