Feature Reviews in Cerebrovascular Research

Complex diseases that affect the functioning of the central nervous system pose a major problem for modern society. Among these, ischemic stroke (IS) holds a special place as one of the most common causes of disability and mortality worldwide. Furthermore, Alzheimer’s disease (AD) ranks first among neurodegenerative diseases, drastically reducing brain activity and overall life quality and duration. Recent studies have shown that AD and IS share several common risk and pathogenic factors, such as an overlapping genomic architecture and molecular signature. In this review, we will summarize the genomics and RNA biology studies of IS and AD, discussing the interconnected nature of these pathologies. Additionally, we highlight specific genomic points and RNA molecules that can serve as potential tools in predicting the risks of diseases and developing effective therapies in the future. Full article

Small vessel diseases (SVD) is an umbrella term including several entities affecting small arteries, arterioles, capillaries, and venules in the brain. One of the most relevant and prevalent SVDs is cerebral amyloid angiopathy (CAA), whose pathological hallmark is the deposition of amyloid fragments in the walls of small cortical and leptomeningeal vessels. CAA frequently coexists with Alzheimer’s Disease (AD), and both are associated with cerebrovascular events, cognitive impairment, and dementia. CAA and AD share pathophysiological, histopathological and neuroimaging issues. The venular involvement in both diseases has been neglected, although both animal models and human histopathological studies found a deposition of amyloid beta in cortical venules. This review aimed to summarize the available information about venular involvement in CAA, starting from the biological level with the putative pathomechanisms of cerebral damage, passing through the definition of the peculiar angioarchitecture of the human cortex with the functional organization and consequences of cortical arteriolar and venular occlusion, and ending to the hypothesized links between cortical venular involvement and the main neuroimaging markers of the disease. Full article

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, neuronal differentiation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation in the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving poststroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury. Full article

This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still very controversial whether the amount of vitamin D taken daily is actually the only problem related to its biological functions. Currently, the plasma concentration of 25-hydroxyvitamin D represents the only indicator of the circulating blood quota. The concept is that the biological function of vitamin D is not only linked to its circulating levels, but it is hypothesized that its biological functions depend, above all, on its total bioavailability. In particular, vitamin D circulates for the most part linked to albumin and vitamin D binding protein (DBP), which depend on various pathological conditions and physiologically, above all, the function of the latter is regulated by estrogens, glucocorticoids, and inflammatory cytokines. During her life, women undergo various changes in the hormonal and sexual sphere concerning menarche, possible pregnancies, and breastfeeding but also the use of contraceptives and, finally, the transition from the period of fertility to menopause. Each of these phases presents specific needs and, consequently, sometimes also specific criticalities. Studies on young women have shown that vitamin D deficiency is present in 58 to 91% of cases. Obesity, metabolic disorders, and variation in estrogen contraction may affect vitamin D deficiency due to the decreased bioavailability from dietary sources due to deposition in body fat compartments. Full article

Anesthesia in neurosurgery embodies a vital element in the development of neurosurgical intervention. This undisputed interest has offered surgeons and anesthesiologists an array of anesthetic selections to utilize, though with this allowance comes the equally essential requirement of implementing a maximally appropriate agent. To date, there remains a lack of consensus and official guidance on optimizing anesthetic choice based on operating priorities including hemodynamic parameters (e.g., CPP, ICP, MAP) in addition to the route of procedure and pathology. In this review, the authors detail the development of neuroanesthesia, summarize the advantages and drawbacks of various anesthetic classes and agents, while lastly cohesively organizing the current literature of randomized trials on neuroanesthesia across various procedures. Full article

Background: Subarachnoid hemorrhage resulting from cerebral aneurysm rupture is a significant cause of morbidity and mortality. Early identification of aneurysms on Computed Tomography Angiography (CTA), a frequently used modality for this purpose, is crucial, and artificial intelligence (AI)-based algorithms can improve the detection rate and minimize the intra- and inter-rater variability. Thus, a systematic review and meta-analysis were conducted to assess the diagnostic accuracy of deep-learning-based AI algorithms in detecting cerebral aneurysms using CTA. Methods: PubMed (MEDLINE), Embase, and the Cochrane Library were searched from January 2015 to July 2023. Eligibility criteria involved studies using fully automated and semi-automatic deep-learning algorithms for detecting cerebral aneurysms on the CTA modality. Eligible studies were assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A diagnostic accuracy meta-analysis was conducted to estimate pooled lesion-level sensitivity, size-dependent lesion-level sensitivity, patient-level specificity, and the number of false positives per image. An enhanced FROC curve was utilized to facilitate comparisons between the studies. Results: Fifteen eligible studies were assessed. The findings indicated that the methods exhibited high pooled sensitivity (0.87, 95% confidence interval: 0.835 to 0.91) in detecting intracranial aneurysms at the lesion level. Patient-level sensitivity was not reported due to the lack of a unified patient-level sensitivity definition. Only five studies involved a control group (healthy subjects), whereas two provided information on detection specificity. Moreover, the analysis of size-dependent sensitivity reported in eight studies revealed that the average sensitivity for small aneurysms (<3 mm) was rather low (0.56). Conclusions: The studies included in the analysis exhibited a high level of accuracy in detecting intracranial aneurysms larger than 3 mm in size. Nonetheless, there is a notable gap that necessitates increased attention and research focus on the detection of smaller aneurysms, the use of a common test dataset, and an evaluation of a consistent set of performance metrics. Full article

The use of periprocedural dual antiplatelet therapy (DAPT) has significantly evolved along with innovations in the endovascular management of intracranial aneurysms. Historically, aspirin and clopidogrel have been the most commonly employed regimen due to its safety and efficacy. However, recent studies highlight the importance of tailoring DAPT regimens to individual patient characteristics which may affect clopidogrel metabolism, such as genetic polymorphisms. In the present report, a systematic review of the literature was performed to determine optimal antiplatelet use with flow diverting stents, intracranial stents, intrasaccular devices, and stent-assisted coiling. Studies were analyzed for the number of aneurysms treated, DAPT regimen, and any thromboembolic complications. Based on inclusion criteria, 368 studies were selected, which revealed the increasing popularity of alternative DAPT regimens with the aforementioned devices. Thromboembolic or hemorrhagic complications associated with antiplatelet medications were similar across all medications. DAPT with ticagrelor, tirofiban, or prasugrel are effective and safe alternatives to clopidogrel and do not require enzymatic activation. Further clinical trials are needed to evaluate different antiplatelet regimens with various devices to establish highest-level evidence-based guidelines and recommendations. Full article

Background: Stroke is a significant public health problem and a leading cause of death and long-term disability worldwide. Several treatments for ischemic stroke have been developed, but these treatments have limited effectiveness. One potential treatment for this condition is Actovegin^®/AODEJIN, a calf blood deproteinized hemodialysate/ultrafiltrate that has been shown to have pleiotropic/multifactorial and possibly multimodal effects. The actual actions of this medicine are thought to be mediated by its ability to reduce oxidative stress, inflammation, and apoptosis and to enhance neuronal survival and plasticity. Methods: To obtain the most up-to-date information on the effects of Actovegin^®/AODEJIN in ischemic stroke, we systematically reviewed the literature published in the last two years. This review builds upon our previous systematic literature review published in 2020, which used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to search for and select related articles over almost two decades, between 1 January 2001 and 31 December 2019. Additionally, we compared the results of our PRISMA search (human intelligence-based) with those obtained from an interrogation of a GPT-based chatbot (ChatGPT) in order to ensure comprehensive coverage of potentially relevant studies. Results: Our updated review found limited new evidence on the use of Actovegin^®/AODEJIN in ischemic stroke, although the number of articles on this subject consistently increased compared to that from our initial systematic literature review. Specifically, we found five articles up to 2020 and eight more until December 2022. While these studies suggest that Actovegin^®/AODEJIN may have neuroprotective effects in ischemic stroke, further clinical trials are needed to confirm these findings. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Discussion: Our funnel analysis showed no evidence of publication bias, suggesting that the limited number of studies identified was not due to publication bias but rather due to a lack of research in this area. However, there are limitations when using ChatGPT, particularly in distinguishing between truth and falsehood and determining the appropriateness of interpolation. Nevertheless, AI can provide valuable support in conducting PRISMA-type systematic literature reviews, including meta-analyses. Conclusions: The limited number of studies identified in our review highlights the need for additional research in this area, especially as no available therapeutic agents are capable of curing central nervous system lesions. Any contribution, including that of Actovegin (with consideration of a positive balance between benefits and risks), is worthy of further study and periodic reappraisal. The evolving advancements in AI may play a role in the near future. Full article