Search Results (87)

Background/Objectives: A growing body of evidence is amassing in the literature suggesting a correlation between Alzheimer’s disease (AD) and thrombotic vascular complications, which led to the suggestive hypothesis that thrombosis may contribute to AD onset and progression by damaging the neurovasculature and reducing the cerebral blood flow. In turn, low cerebral blood flow is likely to contribute to neurodegeneration by reducing nutrient and oxygen supply and impairing toxic metabolite removal from the brain tissue. Methods: We searched the literature for studies in animal models of AD or patients diagnosed with the disease that reported circulating markers of platelet hyperactivity or hypercoagulation, or histological evidence of brain vascular thrombosis. Results: Platelet hyperactivity and hypercoagulability have been described in multiple animal models of AD, and histological evidence of neurovascular thrombosis has also been reported. Similarly, clinical studies on patients with AD showed circulating markers of platelet hyperactivity and hypercoagulation, or histological evidence of neurovascular thrombosis collected from post-mortem brain tissue samples. Conclusions: Taken together, a convincing picture is emerging that suggests a strong correlation between systemic or neurovascular thrombosis and AD. Nonetheless, a mechanistic role for haemostasis dysregulation and neurovascular damage in the onset or the progression of AD remains to be proven. Future research should focus on this important question in order to clarify the mechanisms underlying AD and identify a treatment for this disease. Full article

Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0–300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. Methods: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. Results: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. Conclusions: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply. Full article

Increases in flow elicit dilations in the basilar artery (BA) supplied by the posterior cerebral circulation (PCC), and ensuring efficient blood supply to the circle of Willis in which blood flow and pressure can distribute and equalize, and thus provide the appropriate supply for the daughter branches to reach certain brain areas. In contrast, increases in flow elicit constrictions in the middle cerebral artery (MCA), supplied by the anterior cerebral circulation (ACC) and regulating the blood pressure and flow in distal cerebral circulation. Mediators of flow-dependent responses include arachidonic acid (AA) metabolites and nitric oxide (NO). We hypothesized that mediators of flow-dependent responses are differentially expressed in cerebral arteries of the PCC (CA_PCC) and ACC (CA_ACC). The expressions of key enzymes of the AA pathway—cyclooxygenases (COX1/COX2), cytochrome P450 hydroxylases (Cyp450), thromboxane synthase (TXAS), thromboxane A2 (TP) receptor, prostacyclin synthase (PGIS), prostacyclin (IP) receptor (IP); neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS)—in the BA and MCA from rats (n = 20) were determined by western blotting. Transcriptome analysis in CA_PCC and CA_ACC from rats (n = 25) was assessed by RNA sequencing. In BA compared to MCA, COX1/2 and Cyp450 protein expressions were lower, PGIS was higher, TXAS and nNOS/eNOS were similar, TP receptors were lower, and IP receptors were higher. Gene expressions of vasodilator canonical pathways were higher in CA_PCC; vasoconstriction canonical pathways were higher in CA_ACC. Mediators of flow-dependent vasomotor signaling are differentially expressed in cerebral arteries of the posterior and anterior circulation, corresponding to their vasomotor function. Full article

Cerebral ischemia is a pathological condition characterized by complete blood and oxygen supply deprivation to neuronal tissue. The ischemic brain compensates for the rapid decline in ATP levels by increasing the anaerobic glycolysis rate, which leads to lactate accumulation and subsequent acidosis. Astrocytes play a critical role in regulating cerebral energy metabolism. Mitochondria are significant targets in hypoxia-ischemia injury, and disruptions in mitochondrial homeostasis and cellular energetics worsen outcomes, especially in the elderly. Elevated levels of n-3 polyunsaturated fatty acids (PUFAs) protect the adult and neonatal brain from ischemic damage by suppressing inflammation, countering oxidative stress, supporting neurovascular unit reconstruction, and promoting oligodendrogenesis. This study examines extra virgin olive oil (EVOO) treatment on TNC WT and TNC M23 cells, focusing on oxygen consumption and reactive oxygen species (ROS) production. This study investigates the effects of different durations of middle cerebral artery occlusion (MCAo) and EVOO administration on cerebral infarct volume, neurological scores, mitochondrial function, and cell viability. Cerebral infarct volume increased with longer ischemia times, while EVOO treatment (0.5 mg/kg/day) significantly reduced infarction across all MCAo durations. The oxygen consumption assays demonstrate EVOO’s dose-dependent stimulation of mitochondrial respiration in astrocytes, particularly at lower concentrations. Furthermore, EVOO-treated cells reduce ROS production during hypoxia, improve cell viability under ischemic stress, and enhance ATP production in ischemic conditions, underscoring EVOO’s neuroprotective potential. Full article

Neurovascular coupling (NVC) refers to the process of local changes in cerebral blood flow (CBF) after neuronal activity, which ensures the timely and adequate supply of oxygen, glucose, and substrates to the active regions of the brain. Recent clinical imaging and experimental technology advancements have deepened our understanding of the cellular mechanisms underlying NVC. Pathological conditions such as stroke, subarachnoid hemorrhage, cerebral small vascular disease, and vascular cognitive impairment can disrupt NVC even before clinical symptoms appear. However, the complexity of the underlying mechanism remains unclear. This review discusses basic and clinical experimental evidence on how neural activity sensitively communicates with the vasculature to cause spatial changes in blood flow in cerebrovascular diseases. A deeper understanding of how neurovascular unit-related cells participate in NVC regulation is necessary to better understand blood flow and nerve activity recovery in cerebrovascular diseases. Full article

Background: The external carotid artery (ECA) supplies blood to various facial and neck regions and may contribute to collateral cerebral perfusion. With the rise in carotid artery stenting (CAS) as a treatment for carotid stenosis, ECA overstenting has become a common procedure feature. This study aimed to assess the incidence, characteristics, and duration of facial pain following CAS, hypothesizing that ECA overstenting may contribute to facial pain. Materials and Methods: This prospective study included 55 patients treated with CAS for internal carotid artery (ICA) stenosis at a single center. Patients’ facial pain was evaluated using a numeric rating scale (NRS) before, immediately after, and 24 h post-CAS. Patient data, including demographics, comorbidities, and procedural details, were analyzed to assess the relationship between ICA stenosis degree, ECA diameter changes, and facial pain incidence. Results: CAS was associated with intraoperative facial pain in 27.27% of patients, with 7.28% reporting residual pain 24 h post-procedure. Pain occurrence was significantly higher in patients with lower ICA stenosis (p = 0.04). The median ECA diameter decreased from 4.11 mm to 3.16 mm (p < 0.001) after CAS, with ECA overstenting observed in 96.4% of cases. No significant relationship was found between pain severity and stent width or length. Conclusions: This study highlights that CAS significantly decreases the diameter of ECA. Additionally, ECA overstenting might be associated with perioperative and postoperative facial pain, emphasizing the need for careful monitoring of ECA patency following CAS. Full article

Compared with other organs in the body, the human brain is extremely sensitive to changes in O₂ and CO₂ levels. This study applied functional near-infrared spectroscopy (fNIRS) to analyze the changes in cerebral oxygen saturation (COS) and hemoglobin (Hb) concentrations in response to various atmospheric gas concentrations and investigate their effects on brain function. Twenty-nine adults were exposed to four gas conditions, namely atmospheric concentration (C1), high O₂ concentration (C2), high CO₂ concentration (C3), and high O₂ and CO₂ concentrations (C4). Changes in COS and Hb concentrations were measured using fNIRS, whereas heart rate (HR) and percutaneous oxygen saturation (SpO₂) were measured using a patient monitor. COS, oxy-Hb (HbO), and total-Hb (HbT) increased progressively from C1 to C4, whereas deoxy-Hb (HbR) exhibited a decreasing trend. Moreover, the COS and Hb concentrations were more strongly influenced by high CO₂ levels than by high O₂ levels. High O₂ concentrations increased the blood O₂ saturation, whereas high CO₂ concentrations increased blood flow as a physiological response, enhancing O₂ delivery to the brain. Additionally, HR and SpO₂ increased at high CO₂ concentrations. However, at high O₂ concentrations providing a sufficient O₂ supply, SpO₂ increased while HR decreased. Therefore, adjusting the concentrations of CO₂ and O₂ may improve cerebral blood flow and change brain function, supporting cerebrovascular health and preventing related diseases. Full article

Cognitive impairment is a major healthcare challenge worldwide, with vascular cognitive impairment (VCI) being its second leading cause after Alzheimer’s disease. VCI is a heterogeneous group of cognitive disorders resulting from various vascular pathologies. Therefore, it is particularly difficult to determine its underlying cause and exact molecular basis. Nevertheless, the current understanding of the pathophysiological processes underlying VCI has changed and evolved in the last decades. The aim of this narrative review is to summarize the current state of knowledge on VCI pathogenesis and to analyze the potential role of the gut microbiota in this process, considering the most recent scientific reports and in accordance with the current understanding of these processes. Chronic cerebral hypoperfusion, which results in impaired blood supply, i.e., oxygen and nutrient deficiency, is the main underlying mechanism of VCI. Furthermore, chronic cerebral hypoperfusion triggers a cascade of molecular changes, starting with an energy imbalance, leading to glutamate excitotoxicity, acidotoxicity, and oxidative stress. Also, all of the above provoke the activation of microglia and the release of pro-inflammatory cytokines that recruit systemic immune cells and lead to their infiltration into the central nervous system, resulting in neuroinflammation. Blood–brain barrier dysfunction may occur at various stages of chronic cerebral hypoperfusion, ultimately increasing its permeability and allowing potentially toxic substances to enter the brain parenchyma. Gut microbiota and their metabolites, which have been identified in numerous inflammatory conditions, may also influence the pathophysiological processes of VCI. Full article

The Bawean deer (Axis kuhlii) is a small deer species endemic to the island of Bawean in Indonesia. The species is listed as critically endangered by the IUCN Red List. The current population is assessed to be less than 500 adults living in the wild. The cerebral arterial circle (also called the circle of Willis) is an anastomosis of arteries that supply the brain. The aim of this study was to describe the arterial vascularization of the brain in this species. Three different methods were used to obtain a complete arterial pattern of this region—latex injection, corrosion cast, and contrast-enhanced computed tomography. The arterial vascularization of the brain was described. The pattern of the arterial vessels supplying the brain in this species was similar to that described previously by ruminants. The vessel with the biggest lumen branching off from the circle of Willis was the medial cerebral artery. The basilar artery is a vessel with a narrow lumen and does not mediate the delivery of blood to the encephalon from the caudal side. The results of the study may be useful in creating veterinary protocols for treating vascular diseases in this species and further studies from the field of pathophysiology or pathology. Full article

Children and adolescents (C&As) with congenital heart defects (CHDs) have decreased functional capacity and executive functioning (EF) due to brain abnormalities and decreased cerebral perfusion. Exercise may improve EF via increased cognitive demands and cerebral blood supply. The purpose of this review was to identify evidence describing the impact of physical activity (PA) interventions on EF in C&As with CHDs. The following databases were searched from 2000 to 2024: MEDLINE, EMBASE, CINAHL, Scopus, CENTRAL, and PsycInfo. The inclusion criteria consisted of participants aged from birth to 18 years with CHD, interventions related to PA, and EF as an outcome measure. Articles were excluded if adults were included, translation to English was impossible, and full access was unavailable. Of 613 initial articles, 3 were analyzed, with only 1 meeting all inclusion criteria. The included study found significant improvements in self-reported cognitive functioning and parent-reported social functioning after 12 weeks of aerobic exercise in children aged 10–15 years with CHDs. Common themes among the reviewed articles indicated that EF remains impaired throughout the lifespan, children have unique interventional and developmental needs, and research remains limited despite theoretical benefits. Further investigation of the effect of PA on EF in C&As with CHDs is needed. Full article

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70–140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier. Full article

Cerebral ischemia-reperfusion injury (IRI), occurring after blood supply restoration, contributes significantly to stroke-related deaths. This study explored the combined impact and mechanisms of astragaloside IV (AS-IV), hydroxysafflor yellow A (HSYA), and their combination in mitigating IRI. Male Sprague–Dawley (SD) rats were randomized to the Sham, MCAO, MCAO+AS-IV, MCAO+HSYA, and MCAO+AS-IV+HSYA groups. Neurological deficits and cerebral infarction were examined after restoring the blood supply to the brain. Pathomorphological changes in the cerebral cortex were observed via HE staining. IL-1β and IL-18 were quantified using ELISA. The expression of NF-κB and GSDMD in the ischemic cerebrum was analyzed using immunohistochemistry. The expression levels of NLRP3, ASC, IL-1β, Caspase-1, and GSDMD in the ischemic cerebrum were evaluated using Western blot. The MCAO+AS-IV, MCAO+HSYA, and MCAO+AS-IV+HSYA groups exhibited notably better neurological function and cerebral infarction compared with the MCAO group. The combined treatment demonstrated superior brain tissue injury alleviation. Reductions in NF-κB, GSDMD positive cells, and NLRP3/ASC/IL-1β/Caspase-1/GSDMD protein expression in the ischemic brain were significantly more pronounced with the combined therapy, indicating a synergistic effect in countering cerebral IRI via the NF-κB/NLRP3/Caspase-1/GSDMD pathway inhibition of cell pyroptosis-induced injury. Full article

The cerebellum, a major feature of the hindbrain, lies posterior to the pons and medulla and inferior to the posterior part of the cerebrum. It lies beneath the tentorium cerebelli in the posterior cranial fossa and consists of two lateral hemispheres connected by the vermis. The cerebellum is primarily supplied by three arteries originating from the vertebrobasilar system: the superior cerebellar artery (SCA), the anterior inferior cerebellar artery (AICA), and the posterior inferior cerebellar artery (PICA). However, variations of the cerebellar arteries may occur, such as duplication of the SCA, SCA creating a common trunk with the posterior cerebral artery, triplication of the AICA, and agenesis of PICA, amongst others. Knowledge of the arterial anatomy of the cerebellum is crucial, as inadequate blood supply to this region can result in diminished motor functioning, significantly impacting the quality of life for patients. The present study demonstrated the importance of adequate anatomical knowledge of the arteries supplying the cerebellum. The PubMed and Embase databases were searched to gather articles on the anatomical characteristics and variations of the arterial supply of the cerebellum. It is the most comprehensive and up-to-date review available in the literature. The possible variations of these vessels may be clinically silent or present with clinical symptoms such as neurovascular compression syndromes of the cranial nerves and aneurysms. With a comprehensive understanding of the cerebellar arterial system, physicians can enhance their diagnostic and treatment capabilities, ultimately leading to more effective management of cerebellar vascular-related issues and other neurological deficits. Full article

An ischemic stroke, one of the leading causes of morbidity and mortality, is caused by ischemia and hemorrhage resulting in impeded blood supply to the brain. According to many studies, blueberries have been shown to have a therapeutic effect in a variety of diseases. Therefore, in this study, we investigated whether blueberry-treated mesenchymal stem cell (MSC)-derived extracellular vesicles (B-EVs) have therapeutic effects in in vitro and in vivo stroke models. We isolated the extracellular vesicles using cryo-TEM and characterized the particles and concentrations using NTA. MSC-derived extracellular vesicles (A-EVs) and B-EVs were round with a lipid bilayer structure and a diameter of ~150 nm. In addition, A-EVs and B-EVs were shown to affect angiogenesis, cell cycle, differentiation, DNA repair, inflammation, and neurogenesis following KEGG pathway and GO analyses. We investigated the protective effects of A-EVs and B-EVs against neuronal cell death in oxygen–glucose deprivation (OGD) cells and a middle cerebral artery occlusion (MCAo) animal model. The results showed that the cell viability was increased with EV treatment in HT22 cells. In the animal, the size of the cerebral infarction was decreased, and the behavioral assessment was improved with EV injections. The levels of NeuN and neurofilament heavy chain (NFH)-positive cells were also increased with EV treatment yet decreased in the MCAo group. In addition, the number of apoptotic cells was decreased with EV treatment compared with ischemic animals following TUNEL and Bax/Bcl-2 staining. These data suggested that EVs, especially B-EVs, had a therapeutic effect and could reduce apoptotic cell death after ischemic injury. Full article

Brain ischemia is one of the major causes of chronic disability and death worldwide. It is related to insufficient blood supply to cerebral tissue, which induces irreversible or reversible intracellular effects depending on the time and intensity of the ischemic event. Indeed, neuronal function may be restored in some conditions, such as transient ischemic attack (TIA), which may be responsible for protecting against a subsequent lethal ischemic insult. It is well known that the brain requires high levels of oxygen and glucose to ensure cellular metabolism and energy production and that damage caused by oxygen impairment is tightly related to the brain’s low antioxidant capacity. Oxygen is a key player in mitochondrial oxidative phosphorylation (OXPHOS), during which reactive oxygen species (ROS) synthesis can occur as a physiological side-product of the process. Indeed, besides producing adenosine triphosphate (ATP) under normal physiological conditions, mitochondria are the primary source of ROS within the cell. This is because, in 0.2–2% of cases, the escape of electrons from complex I (NADPH-dehydrogenase) and III of the electron transport chain occurring in mitochondria during ATP synthesis leads to the production of the superoxide radical anion (O₂^•−), which exerts detrimental intracellular effects owing to its high molecular instability. Along with ROS, reactive nitrosative species (RNS) also contribute to the production of free radicals. When the accumulation of ROS and RNS occurs, it can cause membrane lipid peroxidation and DNA damage. Here, we describe the intracellular pathways activated in brain tissue after a lethal/sub lethal ischemic event like stroke or ischemic tolerance, respectively, highlighting the important role played by oxidative stress and mitochondrial dysfunction in the onset of the two different ischemic conditions. Full article