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Pathophysiology and Molecular Mechanisms of Acute Stroke
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Pathophysiology and Molecular Mechanisms of Acute Stroke

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 18361

Special Issue Editors

Dr. Adria Arboix

E-Mail Website
Guest Editor
Unit of Cerebrovascular Diseases, Service of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
Interests: cerebrovascular diseases; lacunar strokes; acute stroke; vascular cognitive impairment
Special Issues, Collections and Topics in MDPI journals
Dr. Teresa Gasull

E-Mail Website
Guest Editor
Cellular and Molecular Neurobiology Research Group, Department of Neurosciences, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain
Interests: stroke; iron dyshomeostasis; excitotoxicity; ferroptosis; new-generation therapies; glutamate excitotoxicity; transferrin; free radicals; therapeutic targets; proteomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stroke remains a leading cause of death and disability and has a complex pathophysiology. Increasing evidence suggests that the brain is extremely sensitive to even short-duration ischemia, and that multiple mechanisms are involved in the tissue damage that results from cerebral ischemia. Ischemic stroke initiates a cascade of events including ATP depletion, ionic dysregulation, increased release of glutamate, excess production of free radicals, as well as edema and inflammation; all these events eventually contribute to cell death. In contrast, in intracerebral hemorrhage, the oppression and destruction of brain tissue by hematoma is the primary cause of brain injury, but inflammation, coagulation response, and the toxicity of the released hemoglobin play pivotal roles as well. Cell death after stroke has been attributed mainly to necrosis or apoptosis in the past, but recent reports show the involvement of other newly described forms of cell death.

The goal of this Special Issue is to provide a critical overview of the underlying factors involved in stroke-related brain injury, especially the role of cell signaling in excitotoxicity, inflammation, apoptosis, and newly described types of cell death such as ferroptosis. Gene and protein expression profiles after stroke and neurogenesis, angiogenesis, and neuroplasticity are other important features of strokes; further research of these should lead to a better understanding of the pathophysiology of acute stroke.

We warmly welcome submissions, including original articles and reviews, focusing on these hot topics.

Dr. Adria Arboix
Dr. Teresa Gasull
Guest Editors

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stroke
  • ischemic
  • hemorrhagic
  • neuronal death
  • molecular mechanisms
  • inflammation
  • epigenetics
  • ischemic tolerance
  • ferroptosis
  • free radicals

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Published Papers (8 papers)

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Editorial

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5 pages, 213 KiB  
Editorial
Molecular Mechanisms and Pathophysiology of Acute Stroke: Recent Advances and Controversies
by Teresa Gasull and Adrià Arboix
Curr. Issues Mol. Biol. 2024, 46(4), 2926-2930; https://doi.org/10.3390/cimb46040182 - 27 Mar 2024
Viewed by 921
Abstract
Stroke is a prevalent neurological disorder defined as an abnormality in brain function resulting from the disruption of cerebral circulation [...] Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)

Research

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22 pages, 4113 KiB  
Article
Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia
by Vasily V. Stavchansky, Vadim V. Yuzhakov, Larisa E. Sevan’kaeva, Natalia K. Fomina, Anastasia E. Koretskaya, Alina E. Denisova, Ivan V. Mozgovoy, Leonid V. Gubsky, Ivan B. Filippenkov, Nikolay F. Myasoedov, Svetlana A. Limborska and Lyudmila V. Dergunova
Curr. Issues Mol. Biol. 2024, 46(3), 2071-2092; https://doi.org/10.3390/cimb46030133 - 5 Mar 2024
Viewed by 1252
Abstract
Stroke remains the second leading cause of death worldwide. The development of new therapeutic agents focused on restoring vascular function and neuroprotection of viable tissues is required. In this study the neuroprotective activity of melanocortin-like ACTH(4–7)PGP and ACTH(6–9)PGP peptides was investigated in rat [...] Read more.
Stroke remains the second leading cause of death worldwide. The development of new therapeutic agents focused on restoring vascular function and neuroprotection of viable tissues is required. In this study the neuroprotective activity of melanocortin-like ACTH(4–7)PGP and ACTH(6–9)PGP peptides was investigated in rat brain at 24 h after transient middle cerebral artery occlusion (tMCAO). The severity of ischemic damage, changes in the proliferative activity of neuroglial cells and vascularization of rat brain tissue were analyzed. The administration of peptides resulted in a significant increase in the volume density of neurons in the perifocal zone of infarction compared to rats subjected to ischemia and receiving saline. Immunohistochemical analysis of the proliferative activity of neuroglia cells using PCNA antibodies showed a significant increase in the number of proliferating cells in the penumbra and in the intact cerebral cortex of rats receiving peptide treatment. The effect of peptides on vascularization was examined using CD31 antibodies under tMCAO conditions, revealing a significant increase in the volume density of vessels and their sizes in the penumbra after administration of ACTH(4–7)PGP and ACTH(6–9)PGP. These findings confirm the neuroprotective effect of peptides due to the activation of neuroglia proliferation and the enhancement of collateral blood flow. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)
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12 pages, 1354 KiB  
Article
Thrombomodulin Serum Levels—A Predictable Biomarker for the Acute Onset of Ischemic Stroke
by Andrei-Lucian Zaharia, Dana Tutunaru, Violeta Diana Oprea, Claudiu Elisei Tănase, Ana Croitoru, Bianca Stan, Doina Carina Voinescu, Ana-Maria Ionescu, Camelia Alexandra Coadǎ and Mihaiela Lungu
Curr. Issues Mol. Biol. 2024, 46(1), 677-688; https://doi.org/10.3390/cimb46010044 - 12 Jan 2024
Cited by 1 | Viewed by 1185
Abstract
The early diagnosis of acute ischemic stroke (AIS) can be challenging in cases presenting with a scarcity of clinical signs, normal cerebral imaging in early stages and a lack of specific serum markers. Thrombomodulin has been shown to be associated with cerebrovascular ischemic [...] Read more.
The early diagnosis of acute ischemic stroke (AIS) can be challenging in cases presenting with a scarcity of clinical signs, normal cerebral imaging in early stages and a lack of specific serum markers. Thrombomodulin has been shown to be associated with cerebrovascular ischemic events and can be considered an important biomarker for the acute onset of ischemic stroke. In our study, we compared the serum levels of thrombomodulin (sTM) between a relevant patient group of 70 AIS patients and a control group of patients without AIS admitted into the neurology department between June 2022 and May 2023. sTM levels were measured at 24 h and 48 h after patients’ admissions into the hospital. There was a significant difference between the two groups (AIS: 23.2 ± 9.17 ng/mL vs. controls: 3.64 ± 1.72 ng/mL; p-value < 0.001). sTM values were correlated with the score of neurological deficits, with gender and dyslipidemia. The association of sTM values with the acute onset of AIS as an end point was significant, which allows rapid therapeutic interventions, even in the absence of a well-defined clinical syndrome (AUC = 0.99). Reanalysis of the patients after propensity score matching increased the power of sTM as a biomarker (AUC = 1). sTM represents a potentially useful biomarker to diagnose the onset of an AIS, even in scarce clinical presentations, which makes thrombomodulin a valuable indicator for early treatment initiation. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)
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14 pages, 2747 KiB  
Article
Neuroprotective Effects of Geopung-Chunghyuldan Based on Its Salvianolic Acid B Content Using an In Vivo Stroke Model
by Han-Gyul Lee, Seungwon Kwon, Sang-Kwan Moon, Seung-Yeon Cho, Seong-Uk Park, Woo-Sang Jung, Jung-Mi Park, Chang-Nam Ko and Ki-Ho Cho
Curr. Issues Mol. Biol. 2023, 45(2), 1613-1626; https://doi.org/10.3390/cimb45020104 - 13 Feb 2023
Cited by 5 | Viewed by 2175
Abstract
Background: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD’s effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of [...] Read more.
Background: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD’s effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. Methods: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. Results: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. Conclusions: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)
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16 pages, 2597 KiB  
Article
Development of Post-Stroke Cognitive and Depressive Disturbances: Associations with Neurohumoral Indices
by Marina Y. Zhanina, Tatyana A. Druzhkova, Alexander A. Yakovlev, Elena E. Vladimirova, Sofia V. Freiman, Natalia N. Eremina, Alla B. Guekht and Natalia V. Gulyaeva
Curr. Issues Mol. Biol. 2022, 44(12), 6290-6305; https://doi.org/10.3390/cimb44120429 - 11 Dec 2022
Cited by 12 | Viewed by 2302
Abstract
Neuropsychiatric complications, in particular cognitive and depressive disorders, are common consequences of ischemic stroke (IS) and complicate the rehabilitation, quality of life, and social adaptation of patients. The hypothalamic–pituitary–adrenal (HPA) system, sympathoadrenal medullary system (SAMS), and inflammatory processes are believed to be involved [...] Read more.
Neuropsychiatric complications, in particular cognitive and depressive disorders, are common consequences of ischemic stroke (IS) and complicate the rehabilitation, quality of life, and social adaptation of patients. The hypothalamic–pituitary–adrenal (HPA) system, sympathoadrenal medullary system (SAMS), and inflammatory processes are believed to be involved in the pathogenesis of these disorders. This study aimed to explore these systems in IS patients, including those with post-stroke cognitive and depressive disorders, within a year after IS. Indices of the HPA axis, inflammatory system, and SAMS were measured in blood serum (cortisol, interleukin-6 (IL-6)), plasma (adrenocorticotropic hormone), and saliva (cortisol, α-amylase). During one year after mild/moderate IS (NIHSS score 5.9 ± 4.3), serum cortisol and salivary α-amylase levels remained elevated in the total cohort. In the group with further cognitive decline, serum and salivary cortisol levels were elevated during the acute period of IS. In the group with poststroke depressive disorder, salivary α-amylase was constantly elevated, while serum IL-6 was minimal during the acute period. The results suggest prolonged hyperactivation of the HPA axis and SAMS after IS. Specifically, post-stroke cognitive impairment was associated with hyperactivation of the HPA axis during the acute IS period, while post-stroke depressive disorder was associated with the chronic inflammatory process and hyperactivation of SAMS during the follow-up period. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)
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14 pages, 1766 KiB  
Article
Serum Levels of VEGF-A and Its Receptors in Patients in Different Phases of Hemorrhagic and Ischemic Strokes
by Anastasiya S. Babkina, Mikhail Ya. Yadgarov, Irina V. Ostrova, Vladislav E. Zakharchenko, Artem N. Kuzovlev, Andrey V. Grechko, Maxim A. Lyubomudrov and Arkady M. Golubev
Curr. Issues Mol. Biol. 2022, 44(10), 4888-4901; https://doi.org/10.3390/cimb44100332 - 14 Oct 2022
Cited by 5 | Viewed by 2275
Abstract
Vascular endothelial growth factors (VEGFs) are important regulators of angiogenesis, neuroprotection, and neurogenesis. Studies have indicated the association of VEGF dysregulation with the development of neurodegenerative and cerebrovascular diseases. We studied the changes in serum levels of VEGF-A, VEGFR-1, and VEGFR-2 in patients [...] Read more.
Vascular endothelial growth factors (VEGFs) are important regulators of angiogenesis, neuroprotection, and neurogenesis. Studies have indicated the association of VEGF dysregulation with the development of neurodegenerative and cerebrovascular diseases. We studied the changes in serum levels of VEGF-A, VEGFR-1, and VEGFR-2 in patients at various phases of ischemic and hemorrhagic strokes. Quantitative assessment of VEGF-A, VEGFR-1, and VEGFR-2 in serum of patients with hemorrhagic or ischemic stroke was performed by enzyme immunoassay in the hyper-acute (1–24 h from the onset), acute (up to 1–7 days), and early subacute (7 days to 3 months) phases of stroke, and then compared with the control group and each other. Results of our retrospective study demonstrated different levels of VEGF-A and its receptors at various phases of ischemic and hemorrhagic strokes. In ischemic stroke, increased VEGFR-2 level was found in the hyper-acute (p = 0.045) and acute phases (p = 0.024), while elevated VEGF-A and reduced VEGFR-1 levels were revealed in the early subacute phase (p = 0.048 and p = 0.012, respectively). In hemorrhagic stroke, no significant changes in levels of VEGF-A and its receptors were identified in the hyper-acute phase. In the acute and early subacute phases there was an increase in levels of VEGF-A (p < 0.001 and p = 0.006, respectively) and VEGFR-2 (p < 0.001 and p = 0.012, respectively). Serum levels of VEGF-A and its receptors in patients with hemorrhagic and ischemic stroke indicate different pathogenic pathways depending on the phase of the disease. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)
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Review

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19 pages, 325 KiB  
Review
Therapeutic Use and Chronic Abuse of CNS Stimulants and Anabolic Drugs
by Daniela Coliță, Cezar-Ivan Coliță, Dirk M. Hermann, Eugen Coliță, Thorsten R. Doeppner, Ion Udristoiu and Aurel Popa-Wagner
Curr. Issues Mol. Biol. 2022, 44(10), 4902-4920; https://doi.org/10.3390/cimb44100333 - 15 Oct 2022
Cited by 5 | Viewed by 5006
Abstract
The available evidence suggests that affective disorders, such as depression and anxiety, increase risk for accelerated cognitive decline and late-life dementia in aging individuals. Behavioral neuropsychology studies also showed that cognitive decline is a central feature of aging impacting the quality of life. [...] Read more.
The available evidence suggests that affective disorders, such as depression and anxiety, increase risk for accelerated cognitive decline and late-life dementia in aging individuals. Behavioral neuropsychology studies also showed that cognitive decline is a central feature of aging impacting the quality of life. Motor deficits are common after traumatic brain injuries and stroke, affect subjective well-being, and are linked with reduced quality of life. Currently, restorative therapies that target the brain directly to restore cognitive and motor tasks in aging and disease are available. However, the very same drugs used for therapeutic purposes are employed by athletes as stimulants either to increase performance for fame and financial rewards or as recreational drugs. Unfortunately, most of these drugs have severe side effects and pose a serious threat to the health of athletes. The use of performance-enhancing drugs by children and teenagers has increased tremendously due to the decrease in the age of players in competitive sports and the availability of various stimulants in many forms and shapes. Thus, doping may cause serious health-threatening conditions including, infertility, subdural hematomas, liver and kidney dysfunction, peripheral edema, cardiac hypertrophy, myocardial ischemia, thrombosis, and cardiovascular disease. In this review, we focus on the impact of doping on psychopathological disorders, cognition, and depression. Occasionally, we also refer to chronic use of therapeutic drugs to increase physical performance and highlight the underlying mechanisms. We conclude that raising awareness on the health risks of doping in sport for all shall promote an increased awareness for healthy lifestyles across all generations. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)

Other

12 pages, 2214 KiB  
Case Report
Stroke-Associating Acute Limb Ischemia Due to the Rupture of a Hydatid Cyst
by Mihaela Lungu, Violeta Diana Oprea, Andrei Lucian Zaharia, Bianca Stan, Laura Rebegea, Dan Iulian Mocanu, Eva Maria Elkan, Elena Niculet and Ana Croitoru
Curr. Issues Mol. Biol. 2023, 45(3), 2597-2608; https://doi.org/10.3390/cimb45030170 - 22 Mar 2023
Viewed by 2171
Abstract
(1) Background: Hydatidosis, or human cystic echinococcosis, is a zoonotic disease. Endemic in some areas, recently it has an increasing incidence in wider regions, determined by population migration. Clinical features depend on the localization and level of infection: asymptomatic or with signs related [...] Read more.
(1) Background: Hydatidosis, or human cystic echinococcosis, is a zoonotic disease. Endemic in some areas, recently it has an increasing incidence in wider regions, determined by population migration. Clinical features depend on the localization and level of infection: asymptomatic or with signs related to hypersensitivity, organic functional deficiencies, expanding mass effects, cyst infection and sudden death. In rare cases, the rupture of a hydatid cyst causes emboli formation by the residual laminated membrane. (2) Methods: We performed an extensive literature review, starting from the case of a 25-year-old patient presenting with neurologic symptoms relevant for acute stroke, associating right upper limb ischemia. (3) Results: Imaging investigations revealed the source of the emboli as the rupture of a hydatid cyst, the patient presenting multiple pericardial and mediastinal localizations. Cerebral imaging confirmed an acute left occipital ischemic lesion, with complete recovery of the neurological deficit after therapy, while surgery for acute brachial artery ischemia had a favorable postoperative evolution. Specific anthelmintic therapy was initiated. An extensive literature review using available databases revealed the scarcity of data on embolism as a consequence of cyst rupture, highlighting the significant risk of clinicians overlooking this possible etiology. (4) Conclusions: An associated allergic reaction should raise the hypothesis of a hydatid cyst rupture as a cause of any level acute ischemic lesion. Full article
(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)
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