scholarly journals New Candidates for Biomarkers and Drug Targets of Ischemic Stroke—A First Dynamic LC-MS Human Serum Proteomic Study

2022 ◽  
Vol 11 (2) ◽  
pp. 339
Author(s):  
Aleksandra Turek-Jakubowska ◽  
Janusz Dębski ◽  
Maciej Jakubowski ◽  
Ewa Szahidewicz-Krupska ◽  
Jakub Gawryś ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Heat Shock ◽  
Acute Ischemic Stroke ◽  
Human Serum ◽  
Acute Phase ◽  
Drug Targets ◽  
Control Group ◽  
Proteomic Study ◽  
Novel Drug ◽  
Novel Drug Targets

(1) Background: The aim of this dynamic-LC/MS-human-serum-proteomic-study was to identify potential proteins-candidates for biomarkers of acute ischemic stroke, their changes during acute phase of stroke and to define potential novel drug-targets. (2) Methods: A total of 32 patients (29–80 years) with acute ischemic stroke were enrolled to the study. The control group constituted 29 demographically-matched volunteers. Subjects with stroke presented clinical symptoms lasting no longer than 24 h, confirmed by neurological-examination and/or new cerebral ischemia visualized in the CT scans (computed tomography). The analysis of plasma proteome was performed using LC-MS (liquid chromatography–mass spectrometry). (3) Results: Ten proteins with significantly different serum concentrations between groups volunteers were: complement-factor-B, apolipoprotein-A-I, fibronectin, alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, heat-shock-cognate-71kDa protein/heat-shock-related-70kDa-protein-2, thymidine phosphorylase-2, cytoplasmic-tryptophan-tRNA-ligase, ficolin-2, beta-Ala-His-dipeptidase. (4) Conclusions: This is the first dynamic LC-MS study performed on a clinical model which differentiates serum proteome of patients in acute phase of ischemic stroke in time series and compares to control group. Listed proteins should be considered as risk factors, markers of ischemic stroke or potential therapeutic targets. Further clinical validation might define their exact role in differential diagnostics, monitoring the course of the ischemic stroke or specifying them as novel drug targets.

scholarly journals Novel Drug Targets for Ischemic Stroke Identified Through Mendelian Randomization Analysis of the Blood Proteome

Circulation ◽  
2019 ◽  
Vol 140 (10) ◽  
pp. 819-830 ◽  
Author(s):  
Michael Chong ◽  
Jennifer Sjaarda ◽  
Marie Pigeyre ◽  
Pedrum Mohammadi-Shemirani ◽  
Ricky Lali ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Drug Targets ◽  
Mendelian Randomization ◽  
Mendelian Randomization Analysis ◽  
Novel Drug ◽  
Randomization Analysis ◽  
Novel Drug Targets

scholarly journals INJECTED CITICOLINE IMPROVES IMPAIRMENT AND DISABILITY DURING ACUTE PHASE TREATMENT IN ISCHEMIC STROKE PATIENTS

2016 ◽  
Vol 51 (4) ◽  
pp. 245
Author(s):  
Rino Wahyudi ◽  
Didik Hasmono ◽  
Ruhaya Fitrina ◽  
Khairil Armal
Keyword(s):  
Ischemic Stroke ◽  
Treatment Group ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Barthel Index ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rank Test ◽  
Control Group ◽  
Before And After ◽  
Acute Phase Treatment

Treatment strategy of ischemic stroke is to reduce the extent of the damage and rescue neurons from death in the early days of ischemic events. Recombinant Tissue-Plasminogen Activator (r-TPA) is the only recommended therapy, but their use is very limited. Citicoline is a neuroprotectant with a therapeutic effect on several stages of the ischemic cascade. However, its use is still being debated. The purpose of this study was to analyze the use of supplementation citicoline injection in patients with acute ischemic stroke in relations to differences in changes in the level of interference (impairment), rate limitation (disability) and the level of obstruction (handicap) between the group receiving supplementation of citicoline injection 2x500 mg iv and the group without supplementation during acute phase treatment. This study was a prospective cohort study using experimental design in patients with acute ischemic stroke who met the inclusion and exclusion criteria with or without supplementation citicoline between January - April 2015 in the National Stroke Hospital, Bukittinggi. Rate of interference was assessed with NIHSS, level of limitations with Barthel Index, and level of obstruction with modified Rankin Scale. Assessment was done 2 times, before and after the treatment. Statistical methods used in this study were Wilcoxon signed rank test, paired T-test and Mann-Whitney test. This study was conducted on 50 subjects divided into 2 groups, a control group without supplementation and group treated with injected citicoline of 2x500 mg iv. Demographic and baseline characteristics did not differ between groups. There were differences in level of interference changes. Mean decrease in control group was 0.96 ± 1.74 NIHSS, while that in treatment group was 2.84 ± 1.46 NIHSS (p <0.05). There were differences in changes in the level of limitations. Mean increase of Barthel Index in control group 9.60 ± 11.17 and in treatment group 20.40 ± 13.99 (p <0.05). However, changes in the level obstacle showed no difference. In conclusion, citicoline injection supplementation in patients with ischemic stroke during acute phase treatment showed improvement differences in changes in the level of distraction (impairment) and the rate limitations (disability), but showed no difference in changes in the level of obstruction (handycaps).

scholarly journals Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Han-Lin Wang ◽  
Jia-Wei Chen ◽  
Shih-Hung Yang ◽  
Yu-Chun Lo ◽  
Han-Chi Pan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Metabolic Rate ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Laser Speckle ◽  
Control Group ◽  
Post Stroke ◽  
Optical Intrinsic Signal ◽  
Penumbra Region ◽  
Anti Inflammation

Administration of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) has been demonstrated to alleviate infarction following ischemic stroke. Reportedly, the main effect of AUDA is exerting anti-inflammation and neovascularization via the inhibition of soluble epoxide hydrolase. However, the major contribution of this anti-inflammation and neovascularization effect in the acute phase of stroke is not completely elucidated. To investigate the neuroprotective effects of AUDA in acute ischemic stroke, we combined laser speckle contrast imaging and optical intrinsic signal imaging techniques with the implantation of a lab-designed cranial window. Forepaw stimulation was applied to assess the functional changes via measuring cerebral metabolic rate of oxygen (CMRO2) that accompany neural activity. The rats that received AUDA in the acute phase of photothrombotic ischemia stroke showed a 30.5 ± 8.1% reduction in the ischemic core, 42.3 ± 15.1% reduction in the ischemic penumbra (p &lt; 0.05), and 42.1 ± 4.6% increase of CMRO2 in response to forepaw stimulation at post-stroke day 1 (p &lt; 0.05) compared with the control group (N = 10 for each group). Moreover, at post-stroke day 3, increased functional vascular density was observed in AUDA-treated rats (35.9 ± 1.9% higher than that in the control group, p &lt; 0.05). At post-stroke day 7, a 105.4% ± 16.4% increase of astrocytes (p &lt; 0.01), 30.0 ± 10.9% increase of neurons (p &lt; 0.01), and 65.5 ± 15.0% decrease of microglia (p &lt; 0.01) were observed in the penumbra region in AUDA-treated rats (N = 5 for each group). These results suggested that AUDA affects the anti-inflammation at the beginning of ischemic injury and restores neuronal metabolic rate of O2 and tissue viability. The neovascularization triggered by AUDA restored CBF and may contribute to ischemic infarction reduction at post-stroke day 3. Moreover, for long-term neuroprotection, astrocytes in the penumbra region may play an important role in protecting neurons from apoptotic injury.

Novel drug targets in 2019

2020 ◽  
Vol 19 (5) ◽  
pp. 300-300 ◽  
Author(s):  
Sorin Avram ◽  
Liliana Halip ◽  
Ramona Curpan ◽  
Tudor I. Oprea
Keyword(s):  
Drug Targets ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Neurological Outcome ◽  
Artery Occlusion ◽  
Control Group ◽  
Stroke Model ◽  
Primary Endpoints ◽  
Neuroprotective Strategy ◽  
Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

scholarly journals Actigraphic Measurement of the Upper Limbs for the Prediction of Ischemic Stroke Prognosis: An Observational Study

Sensors ◽  
2021 ◽  
Vol 21 (7) ◽  
pp. 2479
Author(s):  
Giuseppe Reale ◽  
Silvia Giovannini ◽  
Chiara Iacovelli ◽  
Stefano Filippo Castiglia ◽  
Pietro Picerno ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Observational Study ◽  
Acute Ischemic Stroke ◽  
Acute Phase ◽  
Stroke Unit ◽  
Prognostic Model ◽  
Recovery Process ◽  
Motor Deficits ◽  
Stroke Patients ◽  
Movement Asymmetry

Background: It is often challenging to formulate a reliable prognosis for patients with acute ischemic stroke. The most accepted prognostic factors may not be sufficient to predict the recovery process. In this view, describing the evolution of motor deficits over time via sensors might be useful for strengthening the prognostic model. Our aim was to assess whether an actigraphic-based parameter (Asymmetry Rate Index for the 24 h period (AR2_24 h)) obtained in the acute stroke phase could be a predictor of a 90 d prognosis. Methods: In this observational study, we recorded and analyzed the 24 h upper limb movement asymmetry of 20 consecutive patients with acute ischemic stroke during their stay in a stroke unit. We recorded the motor activity of both arms using two programmable actigraphic systems positioned on patients’ wrists. We clinically evaluated the stroke patients by NIHSS in the acute phase and then assessed them across 90 days using the modified Rankin Scale (mRS). Results: We found that the AR2_24 h parameter positively correlates with the 90 d mRS (r = 0.69, p < 0.001). Moreover, we found that an AR2_24 h > 32% predicts a poorer outcome (90 d mRS > 2), with sensitivity = 100% and specificity = 89%. Conclusions: Sensor-based parameters might provide useful information for predicting ischemic stroke prognosis in the acute phase.

scholarly journals Identification of Polo-like kinases as potential novel drug targets for influenza A virus

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marie O. Pohl ◽  
Jessica von Recum-Knepper ◽  
Ariel Rodriguez-Frandsen ◽  
Caroline Lanz ◽  
Emilio Yángüez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Drug Targets ◽  
Influenza A ◽  
Novel Drug ◽  
Novel Drug Targets
Sign in / Sign up

Export Citation Format

Share Document