Sulforaphane (SFN) is a phytochemical found in cruciferous vegetables. It has been shown to have many protective effects against many diseases, including multiple types of cancer. SFN is a potent ...activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (ARE) genetic pathway. Upregulation of Nrf2-ARE increases the availability of multiple antioxidants. A substantial amount of preclinical research regarding the ability of SFN to protect the nervous system from many diseases and toxins has been done, but only a few small human trials have been completed. Preclinical data suggest that SFN protects the nervous system through multiple mechanisms and may help reduce the risk of many diseases and reduce the burden of symptoms in existing conditions. This review focuses on the literature regarding the protective effects of SFN on the nervous system. A discussion of neuroprotective mechanisms is followed by a discussion of the protective effects elicited by SFN administration in a multitude of neurological diseases and toxin exposures. SFN is a promising neuroprotective phytochemical which needs further human trials to evaluate its efficacy in preventing and decreasing the burden of many neurological diseases.
Despite decades of research, stroke therapies are limited to recanalization therapies that can only be used on <10% of stroke patients; the vast majority of stroke patients cannot be treated by these ...methods. Even if recanalization is successful, the outcome is often poor due to subsequent reperfusion injury. A major damage mechanism operating in stroke is inflammatory injury due to excessive pro-inflammatory cascades. Many studies have shown that, after stroke, splenic inflammatory cells, including neutrophils, monocytes/macrophages, and lymphocytes, are released and infiltrate the brain, heightening brain inflammation, and exacerbating ischemia/reperfusion injury. Clinical studies have observed spleen contraction in acute stroke patients where functional outcome improved with the gradual recovery of spleen volume. These observations are supported by stroke animal studies that have used splenectomy- or radiation-induced inhibition of spleen function to show spleen volume decrease during the acute phase of middle cerebral artery occlusion, and transfer of splenocytes to stroke-injured brain areas. Thus, activation and release of splenic cells are upstream of excessive brain inflammation in stroke. The development of reversible means of regulating splenic activity offers a therapeutic target and potential clinical treatment for decreasing brain inflammation and improving stroke outcomes.
Purpose
To analyze the characteristics of acute ischemic stroke (AIS) resulting from moyamoya disease (MMD) and intracranial large artery atherosclerotic stenosis (LAS).
Method
This real-world case ...control study enrolled imaging-confirmed AIS patients owing to MMD or LAS hospitalized from January 2015 through September 2020 consecutively. The features of risk factors, peripheral blood, and imaging presentations were compared between the two cohorts.
Results
A total of 191 eligible patients entered into final analysis, including 70 cases with MMD stroke and 121 with LAS stroke. LAS stroke vs. MMD stroke, the ratios of hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia were higher in the former (65.3 vs.12.9%, 65.3% vs. 4.3%, 39.7% vs. 2.9%, and 43.8% vs.12.9%; all
p
< 0.01) as well as baseline plasma arachidonic acid (AA) and adenosine diphosphate (ADP)-stimulated maximum platelet aggregation rates (75.3% vs. 60.8% and 73.1% vs.64.9%, respectively, all
p
< 0.01), which were positively correlated with triglycerides and cholesterol levels, blood glucose, age, and platelet counts (all
p
< 0.01). Classical watershed infarction (WSI) accounted for 87.14% in MMD stroke and 40.49% in LAS stroke, respectively (
p
< 0.01). Almost all of the patients with LAS showed plaques in arterial walls on CTA maps and non-homogeneous thickening with irregular luminal narrowing on HRMRI, while plaques were seldom found in MMD besides homogeneous thickening with regular luminal narrowing.
Conclusions
Differing from LAS stroke, MMD stroke mainly presents with WSI and does not feature with platelet hyper-aggregation and fragmentation of ulcer plaque. Whereby, focusing on perfusion improvement rather than antiplatelets and statins may be the predominant step in MMD-stroke correction.
In vitro liver conservation is an issue of ongoing critical importance in graft transplantation. In this study, we investigated the possibility of augmenting the standard pre-transplant liver ...conservation protocol (University of Wisconsin (UW) cold solution) with the phenothiazines chlorpromazine and promethazine. Livers from male Sprague-Dawley rats were preserved either in UW solution alone, or in UW solution plus either 2.4, 3.6, or 4.8 mg chlorpromazine and promethazine (C+P, 1:1). The extent of liver injury following preservation was determined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the ratio of AST/ALT, morphological changes as assessed by hematoxylin-eosin staining, apoptotic cell death as determined by ELISA, and by expression of the apoptotic regulatory proteins BAX and Bcl-2. Levels of glucose (GLU) and lactate dehydrogenase (LDH) in the preservation liquid were determined at 3, 12, and 24 h after incubation to assess glucose metabolism. Oxidative stress was assessed by levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA), and inflammatory cytokine expression was evaluated with Western blotting. C+P augmentation induced significant reductions in ALT and AST activities; the AST/ALT ratio; as well as in cellular swelling, vacuolar degeneration, apoptosis, and BAX expression. These changes were associated with lowered levels of GLU and LDH; decreased expression of SOD, MDA, ROS, TNF-α, and IL-1β; and increased expression of Bcl-2. We conclude that C+P augments hypothermic preservation of liver tissue by protecting hepatocytes from ischemia-induced oxidative stress and metabolic dysfunction. This result provides a basis for improvement of the current preservation strategy, and thus for the development of a more effective graft conservation method.
The purpose of this minireview is to outline the updates made on the association of Alzheimer's disease (AD) and brain injury. A review of the literature on this subject was conducted that included ...various aspects such as age of onset, severity of head trauma, and genetic influences. The results of this mini-review were that consistent associations of AD risk are seen when the severity of head trauma increases, the lag time decreases and when genetic links are present. Brain injury and AD have a complicated relationship that requires further studies to be fully understood.
Physical exercise is a promising rehabilitative strategy for acute ischemic stroke. Preclinical trials suggest that exercise restores cerebral blood circulation and re-establishes the blood–brain ...barrier’s integrity with neurological function and motor skill improvement. Clinical trials demonstrated that exercise improves prognosis and decreases complications after ischemic events. Due to these encouraging findings, early exercise rehabilitation has been quickly adopted into stroke rehabilitation guidelines. Unfortunately, preclinical trials have failed to warn us of an adverse effect. Trials with very early exercise rehabilitation (within 24 h of ischemic attack) found an inferior prognosis at 3 months. It was not immediately clear as to why exercise was detrimental when performed very early while it was ameliorative just a few short days later. This review aimed to explore the potential mechanisms of harm seen in very early exercise administered to acute ischemic stroke patients. To begin, the mechanisms of exercise’s benefit were transposed onto the current understanding of acute ischemic stroke’s pathogenesis, specifically during the acute and subacute phases. Then, exercise rehabilitation’s mechanisms were compared to that of remote ischemic conditioning (RIC). This comparison may reveal how RIC may be providing clinical benefit during the acute phase of ischemic stroke when exercise proved to be harmful.
Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological ...gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes – complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.
Background
Cerebral venous thrombosis (CVT) is easily missed or misdiagnosed in clinical settings because of its high variability in terms of symptoms and radiological findings. Herein, we aimed to ...explore a promising modality for confirming presumed CVT in the hope to uncover its superior diagnostic performance to conventional imaging modalities.
Case presentation: The patient complained of intolerable pain in her forehead and left eye. Her lumbar puncture opening pressure was 140 mmH2O, and her cerebrospinal fluid composition was normal. No marked abnormalities were observed in routine brain images, including non-contrast computed tomography, magnetic resonance imaging, and contrast-enhanced magnetic resonance venography. However, chronic mural thrombi in the lumen of the left cortical veins, transverse/sigmoid sinus, and superior sagittal sinus were identified in magnetic resonance black-blood thrombus imaging (MRBTI) maps.
Conclusions
MRBTI can be used to directly and non-invasively visualize thrombi, and may thus be a promising tool over alternative routine techniques for confirming the diagnosis of CVT.
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