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Advances in the Research of Acute Ischemic Stroke
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Advances in the Research of Acute Ischemic Stroke

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 11917

Special Issue Editor

Dr. Aij Lie Kwan

E-Mail Website
Guest Editor
Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
Interests: neuropathic pain; subarachnoid hemorrhage; peripheral nerve injury; spinal cord injury; traumatic brain injury; neurosurgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stroke has the characteristics of high morbidity, high mortality and high disability rate. It is a major public health concern, ranking as the second leading cause of death and the third leading cause of disability around the world. Acute ischemic stroke refers to the necrosis of brain tissue caused by insufficient blood supply to the brain. Cellular, molecular and metabolomic level research is likely to garner even more attention in the years to come, with stroke incidence increasing in both the aging population and in younger individuals.

The aim of this Research Topic is to cover all aspects of acute ischemic stroke, such as underlying risk factors, etiologies, reperfusion therapy, early secondary prevention, and outcomes. We hope that this Research Topic will generate studies that improve our understanding of acute ischemic stroke and explore novel treatment strategies.

We welcome submissions that report cellular and molecular mechanisms in the onset, progression, treatment strategies, and outcome of acute ischemic stroke.

Dr. Aij Lie Kwan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • acute ischemic stroke
  • stroke
  • cerebral ischemia
  • intracerebral hemorrhage
  • systemic disorder
  • neuroimmune interactions

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Published Papers (5 papers)

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Research

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14 pages, 6125 KiB  
Communication
Tricellulin, α-Catenin and Microfibrillar-Associated Protein 5 Exhibit Concomitantly Altered Immunosignals along with Vascular, Extracellular and Cytoskeletal Elements after Experimental Focal Cerebral Ischemia
by Corinna Höfling, Steffen Roßner, Bianca Flachmeyer, Martin Krueger, Wolfgang Härtig and Dominik Michalski
Int. J. Mol. Sci. 2023, 24(15), 11893; https://doi.org/10.3390/ijms241511893 - 25 Jul 2023
Viewed by 1328
Abstract
Along with initiatives to understand the pathophysiology of stroke in detail and to identify neuroprotective targets, cell-stabilizing elements have gained increasing attention. Although cell culture experiments have indicated that tricellulin, α-catenin and microfibrillar-associated protein 5 (MFAP5) contribute to cellular integrity, these elements have [...] Read more.
Along with initiatives to understand the pathophysiology of stroke in detail and to identify neuroprotective targets, cell-stabilizing elements have gained increasing attention. Although cell culture experiments have indicated that tricellulin, α-catenin and microfibrillar-associated protein 5 (MFAP5) contribute to cellular integrity, these elements have not yet been investigated in the ischemic brain. Applying immunofluorescence labeling, this study explored tricellulin, MFAP5 and α-catenin in non-ischemic and ischemic brain areas of mice (24, 4 h of ischemia) and rats (4 h of ischemia), along with collagen IV and fibronectin as vascular and extracellular matrix constituents and microtubule-associated protein 2 (MAP2) and neurofilament light chain (NF-L) as cytoskeletal elements. Immunosignals of tricellulin and notably MFAP5 partially appeared in a fiber-like pattern, and α-catenin appeared more in a dotted pattern. Regional associations with vascular and extracellular constituents were found for tricellulin and α-catenin, particularly in ischemic areas. Due to ischemia, signals of tricellulin, MFAP5 and α-catenin decreased concomitantly with MAP2 and NF-L, whereby MFAP5 provided the most sensitive reaction. For the first time, this study demonstrated ischemia-related alterations in tricellulin, MFAP5 and α-catenin along with the vasculature, extracellular matrix and cytoskeleton. Confirmatory studies are needed, also exploring their role in cellular integrity and the potential for neuroprotective approaches in stroke. Full article
(This article belongs to the Special Issue Advances in the Research of Acute Ischemic Stroke)
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15 pages, 4053 KiB  
Article
The Role of the Dopamine System in Post-Stroke Mood Disorders in Newborn Rats
by María Villa, María Martínez-Vega, Aarón del Pozo, Itziar Muneta-Arrate, Ana Gómez-Soria, Carolina Muguruza, María de Hoz-Rivera, Angela Romero, Laura Silva, Luis F. Callado, Maria José Casarejos and José Martínez-Orgado
Int. J. Mol. Sci. 2023, 24(4), 3229; https://doi.org/10.3390/ijms24043229 - 6 Feb 2023
Cited by 6 | Viewed by 2131
Abstract
Post-stroke mood disorders (PSMD) affect disease prognosis in adults. Adult rodent models underlie the importance of the dopamine (DA) system in PSMD pathophysiology. There are no studies on PSMD after neonatal stroke. We induced neonatal stroke in 7-day-old (P7) rats by temporal left [...] Read more.
Post-stroke mood disorders (PSMD) affect disease prognosis in adults. Adult rodent models underlie the importance of the dopamine (DA) system in PSMD pathophysiology. There are no studies on PSMD after neonatal stroke. We induced neonatal stroke in 7-day-old (P7) rats by temporal left middle cerebral artery occlusion (MCAO). Performance in the tail suspension test (TST) at P14 and the forced swimming test (FST) and open field test (OFT) at P37 were studied to assess PSMD. DA neuron density in the ventral tegmental area, brain DA concentration and DA transporter (DAT) expression as well as D2 receptor (D2R) expression and G-protein functional coupling were also studied. MCAO animals revealed depressive-like symptoms at P14 associated with decreased DA concentration and reduced DA neuron population and DAT expression. At P37, MCAO rats showed hyperactive behavior associated with increased DA concentration, normalization of DA neuron density and decreased DAT expression. MCAO did not modify D2R expression but reduced D2R functionality at P37. MCAO-induced depressive-like symptoms were reversed by the DA reuptake inhibitor GBR-12909. In conclusion, MCAO in newborn rats induced depressive-like symptoms and hyperactive behavior in the medium and long term, respectively, that were associated with alterations in the DA system. Full article
(This article belongs to the Special Issue Advances in the Research of Acute Ischemic Stroke)
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12 pages, 1461 KiB  
Article
Circulating Inflammatory Biomarkers in Early Prediction of Stroke-Associated Infections
by Isabel M. C. Hasse, Gerrit M. Grosse, Ramona Schuppner, Till Van Gemmeren, Maria M. Gabriel, Karin Weissenborn, Ralf Lichtinghagen and Hans Worthmann
Int. J. Mol. Sci. 2022, 23(22), 13747; https://doi.org/10.3390/ijms232213747 - 9 Nov 2022
Viewed by 1856
Abstract
(1) Background: Patients with acute ischaemic stroke (AIS) are at high risk for stroke-associated infections (SAIs). We hypothesised that increased concentrations of systemic inflammation markers predict SAIs and unfavourable outcomes; (2) Methods: In 223 patients with AIS, blood samples were taken at ≤24 [...] Read more.
(1) Background: Patients with acute ischaemic stroke (AIS) are at high risk for stroke-associated infections (SAIs). We hypothesised that increased concentrations of systemic inflammation markers predict SAIs and unfavourable outcomes; (2) Methods: In 223 patients with AIS, blood samples were taken at ≤24 h, 3 d and 7d after a stroke, to determine IL-6, IL-10, CRP and LBP. The outcome was assessed using the modified Rankin Scale at 90 d. Patients were thoroughly examined regarding the development of SAIs; (3) Results: 47 patients developed SAIs, including 15 lower respiratory tract infections (LRTIs). IL-6 and LBP at 24 h differed, between patients with and without SAIs (IL-6: p < 0.001; LBP: p = 0.042). However, these associations could not be confirmed after adjustment for age, white blood cell count, reduced consciousness and NIHSS. When considering the subgroup of LRTIs, in patients who presented early (≤12 h after stroke, n = 139), IL-6 was independently associated with LRTIs (OR: 1.073, 95% CI: 1.002–1.148). The ROC-analysis for prediction of LRTIs showed an AUC of 0.918 for the combination of IL-6 and clinical factors; (4) Conclusions: Blood biomarkers were not predictive for total SAIs. At early stages, IL-6 was independently associated with outcome-relevant LRTIs. Further studies need to clarify the use of biochemical markers to identify patients prone to SAIs. Full article
(This article belongs to the Special Issue Advances in the Research of Acute Ischemic Stroke)
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18 pages, 1658 KiB  
Article
Hemodynamics and Tissue Optical Properties in Bimodal Infarctions Induced by Middle Cerebral Artery Occlusion
by Chun-Wei Wu, Jia-Jin Chen, Chou-Ching K. Lin, Chien-An Chen, Chun-Ie Wu, Ing-Shiou Hwang, Tsung-Hsun Hsieh, Bor-Shing Lin and Chih-Wei Peng
Int. J. Mol. Sci. 2022, 23(18), 10318; https://doi.org/10.3390/ijms231810318 - 7 Sep 2022
Cited by 6 | Viewed by 2170
Abstract
Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties [...] Read more.
Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties by frequency-domain near-infrared spectroscopy (FD-NIRS), and establish the relationship between cerebral hemodynamics and infarct variation in MCAO model. The rats were undergone transient MCAO using intraluminal filament. The optical properties and hemodynamics were measured by placing the FD-NIRS probes on the scalp of the head before, during, and at various time-courses after MCAO. Bimodal infarction severities were observed after the same 90-min MCAO condition. Significant decreases in concentrations of oxygenated hemoglobin ([HbO]) and total hemoglobin ([HbT]), tissue oxygenation saturation (StO2), absorption coefficient (μa) at 830 nm, and reduced scattering coefficient (μs’) at both 690 and 830 nm were detected during the occlusion in the severe infarction but not the mild one. Of note, the significant increases in [HbO], [HbT], StO2, and μa at both 690 and 830 nm were found on day 3; and increases in μs’ at both 690 and 830 nm were found on day 2 and day 3 after MCAO, respectively. The interhemispheric correlation coefficient (IHCC) was computed from low-frequency hemodynamic oscillation of both hemispheres. Lower IHCCs standing for interhemispheric desynchronizations were found in both mild and severe infarction during occlusion, and only in severe infarction after reperfusion. Our finding supports that sequential FD-NIRS parameters may associated with the severity of the infarction in MCAO model, and the consequent pathologies such as vascular dysfunction and brain edema. Further study is required to validate the potential use of FD-NIRS as a monitor for MCAO verification. Full article
(This article belongs to the Special Issue Advances in the Research of Acute Ischemic Stroke)
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Review

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13 pages, 1696 KiB  
Review
Recent Advances on the Roles of PCSK-9 Inhibitors in the Management of Acute Ischemic Stroke Patients
by Silvina Ilut, Bianca O. Pirlog, Radu Pirlog, Andreea Nutu, Vitalie Vacaras and Sebastian M. Armean
Int. J. Mol. Sci. 2022, 23(18), 10221; https://doi.org/10.3390/ijms231810221 - 6 Sep 2022
Cited by 3 | Viewed by 3649
Abstract
Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current [...] Read more.
Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence. Full article
(This article belongs to the Special Issue Advances in the Research of Acute Ischemic Stroke)
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