Stroke is a major cause of disability for adults over 40 years of age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to a severe stroke injury in a highly regenerative adult mammal. Here we investigate the effects of transient ischemia on adult spiny mice, Acomys cahirinus, due to their ability to regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and Acomys showed rapid behavioral recovery post-stroke yet failed to regenerate impacted brain regions. An Acomys brain atlas in combination with functional (f)MRI demonstrated recovery coincides with neuroplasticity. The strength and quality of the global connectome are preserved post-injury with distinct contralateral and ipsilateral brain regions compensating for lost tissue. Thus, we propose Acomys recovers functionally from an ischemic stroke injury not by tissue regeneration but by altering its brain connectome.

COVID-19 continues to strain healthcare systems around the globe. Research has shown a relationship between COVID-19 and an inflammatory response, including neuropathological outcomes. Additionally, studies have shown positive effects of engagement with music on inflammatory responses; music may have potential, as a method, to reduce inflammation triggered by COVID-19. This review compiles exhaustive research from multiple disciplines to account for this possibility. The authors utilized a meta-narrative approach to complete this review. The search was conducted using PubMed, Embase, OneSearch, Primo, Google Scholar, Clinicaltrials.gov, and the bibliographies of relevant articles. In total, 84 articles were included for full-text review, discussion, and analysis. Articles pertaining to music and acoustics encompassed a date range from 1964–2020. Articles referencing COVID-19 spanned the years 2019–2021. This work focused on associations between engagement with music, stress response, blood-brain barrier integrity, inflammation, COVID-19, and neuropathology in preclinical and clinical models. Detailed analysis revealed that engagement with music has the potential to reduce the harmful effects of COVID-19, particularly in the inflammation and blood clotting pathways associated with a range of pathophysiological and neuropathological issues. Further work is warranted to standardize and validate existing methods associating positive effects of engagement with music on the negative effects of COVID-19.

Ischaemic neurovascular stroke represents a leading cause of death in the developed world. Preclinical and human epidemiological evidence implicates the corticotropin‐releasing factor (CRF) family of neuropeptides as mediators of acute neurovascular injury pathology. Preclinical investigations of the role of CRF, CRF receptors and CRF‐dependent activation of the hypothalamic–pituitary–adrenal (HPA) axis have pointed toward a tissue‐specific and temporal relationship between activation of these pathways and physiological outcomes. Based on the literature, the major phases of ischaemic stroke aetiology may be separated into an acute phase in which CRF and anti‐inflammatory stress signalling are beneficial and a chronic phase in which these contribute to neural degeneration, toxicity and apoptotic signalling. Significant gaps in knowledge remain regarding the pathway, temporality and systemic impact of CRF signalling and stress biology in neurovascular injury progression. Heterogeneity among experimental designs poses a challenge to defining the apparent reciprocal relationship between neurological injury and stress metabolism. Despite these challenges, it is our opinion that the elucidated temporality may be best matched with an antibody against CRF with a half‐life of days to weeks as opposed to minutes to hours as with small‐molecule CRF receptor antagonists. This state‐of‐the‐art review will take a multipronged approach to explore the expected potential benefit of a CRF antibody by modulating CRF and corticotropin‐releasing factor receptor 1 signalling, glucocorticoids and autonomic nervous system activity. Additionally, this review compares the modulation of CRF and HPA axis activity in neuropsychiatric diseases and their counterpart outcomes post‐stroke and assess lessons learned from antibody therapies in neurodegenerative diseases.

Sleep-disordered breathing (SDB) can be a sequela of stroke caused by vascular injury to vital respiratory centers, cerebral edema, and increased intracranial pressure of space-occupying lesions. Likewise, obstructive sleep apnea (OSA) contributes to increased stroke risk through local mechanisms such as impaired ischemic cerebrovascular response and systemic effects such as promoting atherosclerosis, hypercoagulability, cardiac arrhythmias, vascular-endothelial dysfunction, and metabolic syndrome. The impact of OSA on stroke outcomes has been established, yet it receives less attention in national guidelines on stroke management than hyperglycemia and blood pressure dysregulation. Furthermore, whether untreated OSA worsens stroke outcomes is not well-described in the literature. This scoping review provides an updated investigation of the correlation between OSA and stroke, including inter-relational pathophysiology. This review also highlights the importance of OSA treatment and its role in stroke outcomes. Knowledge of pathophysiology, the inter-relationship between these common disorders, and the impact of OSA therapy on outcomes affect the clinical management of patients with acute ischemic stroke. In addition, understanding the relationship between stroke outcomes and pre-existing OSA will allow clinicians to predict outcomes while treating acute stroke.

For years, there have been many discussions about the optimal/beneficial threshold for transfusion of blood products in subarachnoid hemorrhage (SAH), and it remains to be established. Over the period spent by patients who are recuperating from such acute intracranial bleeding, they often become anemic. This is a rationale why these patients are considered candidates for transfusion to restore normal hemoglobin levels and optimal arterial oxygen content. After a comprehensive review of multidisciplinary studies, it becomes evident that the benefits of blood transfusion may vary greatly depending on the situation. The objective here is to summarize the reported outcomes following administration of blood products, i.e., platelets, tranexamic acid, prothrombin complex concentrate, red blood cells, and colloids/crystalloids for optimal oxygenation and to minimize rebleeding. These treatments are reviewed in the context of how they interact with the brain during the early brain injury, the vasospasm, microthrombus formation, inflammation, brain edema, and the delayed cerebral ischemic phases. In severe SAH, cardiac dysfunction and hyponatremia are not uncommon, and the transfusion-associated circulatory overload should be monitored. Thus, continuous hemodynamic monitoring is necessary to prevent pulmonary edema, along with the maintenance of euvolemia. The paper also highlights conditions when transfusion is contraindicated. Patient blood management programs should be promoted to develop clearer hospital transfusion guidelines to strive for optimization of patient hemoglobin and iron stores, and to train for more restrictive RBC policy. The results reported thus far need to be critically reviewed by a panel of experts, along with the need to design novel rigorous prospective parallel-group studies to establish SAH-specific guidelines.

Dexmedetomidine (DEX), an α2-adrenergic agonist, has been widely used for anesthesia, pain control, and intensive care unit sedation. Besides sleep-like sedation, DEX has many other beneficial effects, such as anti-inflammation, antioxidation, and anticell death. Subarachnoid hemorrhage (SAH), a severe and potentially fatal form of stroke, is a complex disease that is divided into 2 phases: early brain injury and delayed cerebral ischemia. In each phase, several pathologic changes are involved, including disturbed intracranial homeostasis, metabolic failure, blood-brain barrier damage, vasospasm, microthrombosis, and cortical spreading depolarization. DEX has been shown to have an effect on these SAH-related pathologic processes. Research shows that DEX could serve as a protective therapy for patients with SAH due to its ability to maintain stable intracerebral homeostasis, balance coagulation-fibrinolysis, repair a damaged blood-brain barrier as well as prevent vasospasm and suppress cortical spreading depolarization by anti-inflammatory, antioxidative, antiapoptotic, and vasoconstriction-dilation effects. In this scoping review, we critically assess the existing data on the potential protective effect of DEX after SAH. So far, only 1 retrospective clinical trial assessing the effect of DEX on clinical outcomes after SAH has been performed. Hence, more trials are still needed as well as translational research bringing results from bench to bedside.

Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH ( p < 1 × 10 −4 ), which require validation. A single variant (rs12949158), in SPNS2 , achieved genome-wide significance ( p = 4.29 × 10 −8 ) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment.

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1–24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.

This review outlines the current clinical research investigating how the haptoglobin (Hp) genetic polymorphism and stroke occurrence are implicated in sickle cell disease (SCD) pathophysiology. Hp is a blood serum glycoprotein responsible for binding and removing toxic free hemoglobin from the vasculature. The role of Hp in patients with SCD is critical in combating blood toxicity, inflammation, oxidative stress, and even stroke. Ischemic stroke occurs when a blocked vessel decreases oxygen delivery in the blood to cerebral tissue and is commonly associated with SCD. Due to the malformed red blood cells of sickle hemoglobin S, blockage of blood flow is much more prevalent in patients with SCD. This review is the first to evaluate the role of the Hp polymorphism in the incidence of stroke in patients with SCD. Overall, the data compiled in this review suggest that further studies should be conducted to reveal and evaluate potential clinical advancements for gene therapy and Hp infusions.

Objective: The aim of this study was to provide the evidence base to guide interconversion of the modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS) in neurological research. Methods: A retrospective analysis of paired mRS and GOS recordings was conducted using datasets with the following selection criteria: (1) patients had haemorrhagic stroke, (2) simultaneous mRS and GOS measurements were available, and (3) data sharing was possible. The relationship between mRS and GOS was assessed using correlation analysis. The optimum dichotomisation thresholds for agreement between the mRS and GOS were identified using Cohen's kappa coefficient. Two-way conversion tables between mRS and GOS were developed based on the highest agreement between scores. Finally, to identify which direction of conversion (mRS to GOS or vice versa) was better, the KolmogorovSmirnov D statistic was calculated. Results: Using 3474 paired recordings the mRS and GOS were shown to be highly correlated (p = 0.90, p < 0.0001). The greatest agreement between the two scoring systems occurred when mRS=0-2 and GOS=4-5 was used to define good outcome (K=0.83, 95% confidence interval: 0.81-0.85). Converting from mRS to GOS was better than the reverse direction as evidenced by a lower Kolmogorov-Smirnov statistic (D=0.054 compared to D=0.157). Conclusions: This study demonstrates that the mRS and GOS are highly correlated, establishes the optimum dichotomisation threshold for agreement, provides a method for interconversion and shows that mRS to GOS conversion is superior to the reverse direction if a choice is available.

The meningeal lymphatic, or glymphatic, system is receiving increasing attention from the scientific community. Recent work includes noninvasive techniques to demonstrate relationships between blood–brain barrier (BBB) activity and the glymphatic system in the human central nervous system. One potential technique is the use of music/sound to enhance BBB permeability regarding the movement of small molecules in and out of the brain. However, there is minimal knowledge regarding the methodical investigation(s) of the uses of music/sound on BBB permeability and glymphatic clearance and the outcomes of these investigation(s). This review contains evidence discussing relationships between music/sound, BBB permeability, and meningeal lymphatic clearance. An overview of the anatomy and physiology of the system is presented. We discuss the uses of music/sound to modulate brain and body functions, highlighting music’s effects on mood and autonomic, cognitive, and neuronal function. We also propose implications for follow-up work. The results showed that music and sound interventions do, in fact, contribute to the opening of the BBB and subsequently increase the function of the meningeal lymphatic system. Evidence also suggests that music/sound has the ability to reduce the collateral effects of brain injuries. Unfortunately, music/sound is rarely used in the clinical setting as a medical intervention. Still, recent research shows the potential positive impacts that music/sound could have on various organ systems.

Over the past several decades, carbon monoxide (CO) has been studied as a potential cytoprotective treatment for neurological diseases. This chapter mainly discusses the mechanisms by which CO is neuroprotective after acute brain injury through Nrf2 and heme oxygenase 1 (HO-1) upregulation. It provides a synopsis of preclinical studies using CO gas or CO-releasing molecules (CORMs) to treat acute brain injuries, including ischemic stroke, neonatal hypoxic-ischemic encephalopathy, hemorrhagic stroke, and traumatic brain injury (TBI). CO gas and CORMs are being tested in clinical trials as putative therapeutic agents for various conditions, including chronic headaches, acute respiratory distress syndrome, vascular disorders, pulmonary fibrosis, chronic obstructive pulmonary disease, pulmonary hypertension, and traumatic brain injury. Finally, clinical trials that use CO gas and CORMs to treat disease in humans are discussed, as will the risks and benefits of beginning clinical trials using CO gas or CORMs to treat acute brain injuries in humans.

Circulating hemopexin is the primary protein responsible for the clearance of heme; therefore, it is a systemic combatant against deleterious inflammation and oxidative stress induced by the presence of free heme. This role of hemopexin is critical in hemolytic pathophysiology. In this review, we outline the current research regarding how the dynamic activity of hemopexin is implicated in sickle cell disease, which is characterized by a pathological aggregation of red blood cells and excessive hemolysis. This pathophysiology leads to symptoms such as acute kidney injury, vaso-occlusion, ischemic stroke, pain crises, and pulmonary hypertension exacerbated by the presence of free heme and hemoglobin. This review includes in vivo studies in mouse, rat, and guinea pig models of sickle cell disease, as well as studies in human samples. In summary, the current research indicates that hemopexin is likely protective against these symptoms and that rectifying depleted hemopexin in patients with sickle cell disease could improve or prevent the symptoms. The data compiled in this review suggest that further preclinical and clinical research should be conducted to uncover pathways of hemopexin in pathological states to evaluate its potential clinical function as both a biomarker and therapy for sickle cell disease and related hemoglobinopathies.

Hemolysis is a physiological condition in which red blood cells (RBCs) lyse, releasing their contents into the extracellular environment. Hemolysis can be a manifestation of several diseases and conditions, such as sickle cell disease, hemorrhagic stroke, and trauma. Heme and hemoglobin are among the unique contents of RBCs that are released into the environment. Although these contents can cause oxidative stress, especially when oxidized in the extracellular environment, they can also initiate a proinflammatory response because they bind to receptors such as the Toll-like receptor (TLR) family. This review seeks to clarify the mechanism by which TLRs initiate a proinflammatory response to heme, hemoglobin, and their oxidized derivatives, as well as the possibility of using soluble TLRs (sTLRs) as therapeutic agents. Furthermore, this review explores the possibility of using sTLRs in hemorrhagic disorders in which mitigating inflammation is essential for clinical outcomes, including hemorrhagic stroke and its subtypes, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH).

Vitamin D supplementation has been shown to improve outcomes for patients suffering from a variety of illnesses such as stroke and cancer. Vitamin D deficiencies have been associated with longer hospital stays, greater severity of symptoms, and death in some complex cases. Due to vitamin D’s burgeoning role in improving patient outcomes, a new sector of research is focusing on the lesser-known implications of vitamin D on health. Traumatic brain injury (TBI) affects approximately 69 million people worldwide per year. Here, we summarize the current scientific understanding of vitamin D dynamics with TBI to elucidate a potential way to lessen the cascade of secondary damage after an initial insult, with the goal of improving overall patient outcomes. Because vitamin D supplementation has been correlated with better outcomes in other pathologies involving immune and inflammatory molecules, it is important to study the potential effect of vitamin D deficiency (VDD) and supplementation on TBI outcomes. Research on vitamin D supplementation in TBI remains in the preliminary stages. There is still much to learn about vitamin D deficiency, dosage, variants of supplementary forms, mechanisms, and its role in TBI.

HomeStrokeVol. 52, No. 9Cerebral Venous Thrombosis and Hypercoagulability Associated With In Vitro Fertilization Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessResearch ArticlePDF/EPUBCerebral Venous Thrombosis and Hypercoagulability Associated With In Vitro Fertilization Amreen B. Farooqui, MD Meghan L. Humbert, DO, MSc Mary Stewart Montague, MD Sylvain Doré, PhD Alexis N. SimpkinsMD, PhD, MSCR Amreen B. FarooquiAmreen B. Farooqui https://orcid.org/0000-0002-4818-5118 Department of Neurology (A.B.F., M.L.H., S.D., A.N.S.), University of Florida College of Medicine, Gainesville. , Meghan L. HumbertMeghan L. Humbert https://orcid.org/0000-0001-8446-5718 Department of Neurology (A.B.F., M.L.H., S.D., A.N.S.), University of Florida College of Medicine, Gainesville. , Mary Stewart MontagueMary Stewart Montague Department of Obstetrics and Gynecology (M.S.M.), University of Florida College of Medicine, Gainesville. , Sylvain DoréSylvain Doré https://orcid.org/0000-0003-3771-5109 Department of Neurology (A.B.F., M.L.H., S.D., A.N.S.), University of Florida College of Medicine, Gainesville. Department of Anesthesiology (S.D.), University of Florida College of Medicine, Gainesville. and Alexis N. SimpkinsAlexis N. Simpkins Correspondence to: Alexis N. Simpkins, MD, PhD, MSCR, University of Florida College of Medicine, 1149 Newell Dr, Rm. L3-100, Gainesville, FL 32611. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7529-4267 Department of Neurology (A.B.F., M.L.H., S.D., A.N.S.), University of Florida College of Medicine, Gainesville. Originally published5 Aug 2021https://doi.org/10.1161/STROKEAHA.121.035962Stroke. 2021;52:e554–e557Case DescriptionA 38-year-old woman with a history of mild headaches presented to an outside facility at 14 weeks of gestation with worsening headaches. The patient's first pregnancy was terminated due to fetal genetic anomalies not compatible with life, and her current pregnancy was achieved by in vitro fertilization (IVF). Her IVF protocol consisted of a period of combined estrogen and progesterone oral contraceptive pills followed by 12 days of follitropin alfa and menotropin injections for ovarian stimulation. After that, she received injections of leuprorelin and choriogonadotropin alfa on the 12th day to trigger ovulation. Her estrogen levels were monitored throughout this process and peaked at 1057 pg/mL just before triggering ovulation. She then underwent oocyte retrieval. After the successful retrieval, she took 2 to 6 mg of estradiol for 46 days while awaiting embryo transfer. Before embryo transfer, she received a dose of progesterone by injection. The estradiol was continued for another 6 days, when she underwent embryo transfer. She was started on intramuscular estradiol and progesterone injections for 2 months for luteal phase support. The day after her last dose of estradiol and progesterone injections, at 14 weeks of gestation, the patient developed a headache different from her typical headaches. The headache was more intense and associated with increased pain when lying flat, impaired focus and concentration, and blurry vision, prompting her to go to her local emergency department. Imaging confirmed a cerebral venous sinus thrombosis (CVST) of the right transverse and sigmoid sinuses and a right temporal lobe hemorrhagic venous infarct (Figure). The patient was discharged on therapeutic dosing of enoxaparin. Five days later, she presented back to the same facility with new-onset nausea and vomiting and subsequently transferred to our facility for further management. Imaging demonstrated stability of the CVST (Figure) and hemorrhagic venous infarct with a mild increase in edema around the hemorrhage. Workup for an alternate etiology of the CVST was negative. She did not have a personal or family history of clotting disorders. After stabilization and improvement in her headaches, she was discharged home to continue the therapeutic doses of enoxaparin.Download figureDownload PowerPointFigure. Cerebral venous thrombosis was diagnosed in a pregnant patient that conceived via in vitro fertilization. Magnetic resonance imaging (MRI) and venography demonstrate thrombosis of right transverse and sigmoid sinuses (A) with associated hemorrhagic venous infarct seen on MRI in the right temporal lobe (B). After the patient's second presentation, repeated imaging at our institution demonstrated that the venous thrombosis (C) and hemorrhagic venous infarct were stable except for slightly more edema within the right temporal lobe (D).DiscussionCVST is an acute occlusion of a central nervous system vein or sinus secondary to thrombus formation.1,2 Although less common than arterial strokes, CVST is an important diagnosis to recognize because it has been reported that ≈3% to 8% of patients may die in the acute phase of the disorder and prognosis is favorable with rapid diagnosis and treatment.1–4 The incidence of CVST in adults varies in the literature, with estimates ranging from 3 to 4 cases per million or 2 to 5 cases per million.1,3 The International Study on Cerebral Vein and Dural Sinus Thrombosis reported that of the 624 adults included in the study, 75% were women, and 20% were pregnant or puerperium. Patients with worse outcomes tend to be male, >37 years of age, and have an intracranial hemorrhage at presentation, central nervous system infection, or deep cerebral venous system thrombosis.4 Approximately 2% of strokes associated with pregnancy are attributed to CVST, with most occurring in the third trimester or the puerperium (6-week period after childbirth).2 Recognizing signs and symptoms suggestive of a CVST can be challenging because presenting symptoms can be variable and nonspecific.1,2 Headache is the most common presenting symptom and occurs in as many as 89% of patients with CVST.1 Neuroimaging is essential for diagnosing CVST. Computed tomographic venography, magnetic resonance venography, or cerebral venography can be used; computed tomographic venography and magnetic resonance venography are the least invasive options.1 If urgent imaging is required, computed tomography should not be delayed or withheld in pregnant patients, although noncontrast magnetic resonance imaging is generally deemed safer because of decreased radiation exposure. Iodinated contrast is thought to be safer than gadolinium because of the risk for accumulation of gadolinium in fetal tissue and amniotic fluid, although fetal effects are unknown.1,5CVST can occur in the setting of primary or inherited thrombophilia (antithrombin III, protein C and S deficiencies, and factor V Leiden), acquired thrombophilias such as thrombocytopenia or disseminated intravascular coagulation, trauma, malignancy, dehydration, or changes in hormone levels caused by pregnancy or oral hormonal supplementation with estrogen.1–4,6,7 Estradiol is an essential sex steroid in women, mainly secreted from ovarian follicles during the follicular phase of the menstrual cycle.8 Exogenous estrogen is used for oral contraception, treatment of symptoms related to menopause, IVF, and gender transitioning.2,3,6 The adverse effects of estrogen are complicated and involve disruption of the balance between procoagulation and anticoagulation factors.3 Other procoagulant risk factors such as increased age, an underlying preexisting hypercoagulable state, and smoking can synergistically increase the hypercoagulability associated with exogenous hormone use.2,3In this case, our patient had several risk factors for developing a pregnancy-related CVST, including the pregnancy itself, age, and the hormone regimen required as part of IVF. There is a rising demand for IVF because women are increasingly delaying childbearing and IVF provides other options for achieving pregnancy for the 10% to 15% of women trying to conceive who experience infertility.7 It is estimated that 5 million babies have been conceived by IVF.7 IVF is accomplished via different protocols, but most involve supplementation with estrogen.8 During the IVF process, hormones are given to trigger ovulation with increased oocyte yield and increase implantation chances.8 During this process, factors II, V, VII, VIII, and IX and fibrinogen levels become elevated.9 IVF is reported to have double the thromboembolism risk relative to pregnancy, with a frequency between 0.8 and 25/1000.7 The risk for venous thromboembolism (VTE) is 5- to 10-fold higher in patients during the first trimester of IVF pregnancies. If patients are hospitalized for ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication of the IVF process, the risk jumps to a 100-fold increase in VTE.7,9 Patients admitted for OHSS are typically started on VTE prophylaxis on admission until they are adequately mobilized.10 It is important to be aware of high-risk patients, such as those with a rapid rise in estradiol level (>3000 pg/mL) and high follicle count (>20 per ovary).10Given the association of CVST with pregnancy and hormonal supplementation, counseling to provide an individualized risk assessment and discuss methods to decrease IVF-associated VTE risk is important. The use of VTE thromboprophylaxis for patients undergoing IVF is debated; however, patients who experience OHSS should be prescribed low-molecular-weight heparin during the first trimester because of the high risk of VTE during this period.7 For patients undergoing IVF who do not experience OHSS, a decision on thromboprophylaxis should be based on the same risk factors as other pregnant patients. Women with previous CVST have a low absolute risk of pregnancy-related venous thrombosis3; however, literature supports the use of low-molecular-weight heparin, in accordance with national guidelines, during pregnancy and puerperium for women who have a history of previous CVST to reduce the risk of recurrent CVST and other thrombotic events.2,3 While warfarin is commonly used to treat CVST in the general population, it is contraindicated in pregnancy because of its teratogenic effects on the fetus.2,10 Current guidelines recommend that anticoagulation be continued for at least 6 months, including at least 6 weeks postpartum.2,3 Novel oral anticoagulants are not currently included in the American Heart Association CVST statement regarding recommendations for CVST treatment outside of pregnancy, and they are not recommended for use during pregnancy.2,3 Patients found to have a CVST associated with pregnancy or IVF should also have diagnostic work to evaluate other possible causes of underlying hypercoagulability and thrombophilia.3 This assessment is particularly important in the context of the coronavirus disease 2019 (COVID-19) pandemic because both the disease and vaccinations have been associated with CVST.Take-Home PointsIVF affords many women the opportunity to conceive; however, providers and patients should have a thorough discussion beforehand regarding the increased risk for VTE (such as CVST) due to supplemental hormones and the hypercoagulable state of pregnancy.The absolute risk for developing VTE during IVF therapy remains low, but it is higher than that in the general population. For those with a history of CVST interested in becoming pregnant, the literature supports consideration of prophylactic low-molecular-weight heparin.Prophylactic anticoagulant use in women receiving IVF is an ongoing debate. For women diagnosed with OHSS during their pregnancy, current guidelines recommend prophylaxis with low-molecular-weight heparin. The duration should be individualized to the patient, and preexisting risk factors for VTE should be considered.AcknowledgmentsAll work was performed in the Departments of Neurology and Anesthesiology at the University of Florida.Sources of FundingNone.Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page e556.Correspondence to: Alexis N. Simpkins, MD, PhD, MSCR, University of Florida College of Medicine, 1149 Newell Dr, Rm. L3-100, Gainesville, FL 32611. Email alexis.[email protected].ufl.eduReferences1. Filippidis A, Kapsalaki E, Patramani G, Fountas KN. Cerebral venous sinus thrombosis: review of the demographics, pathophysiology, current diagnosis, and treatment.Neurosurg Focus. 2009; 27:E3. doi: 10.3171/2009.8.FOCUS09167CrossrefMedlineGoogle Scholar2. Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2011; 42:1158–1192. doi: 10.1161/STR.0b013e31820a8364LinkGoogle Scholar3. Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, Howard VJ, Lichtman JH, Lisabeth LD, Piña IL, et al.; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council for High Blood Pressure Research. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2014; 45:1545–1588. doi: 10.1161/01.str.0000442009.06663.48LinkGoogle Scholar4. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).Stroke. 2004; 35:664–670. doi: 10.1161/01.STR.0000117571.76197.26LinkGoogle Scholar5. Proença F, Guerreiro C, Sá G, Reimão S. Neuroimaging safety during pregnancy and lactation: a review.Neuroradiology. 2021; 63:837–845. doi: 10.1007/s00234-021-02675-1Google Scholar6. Opaskar A, Scharf EL, Chilungu MW, Kelly AG. Transgender venous thrombosis.Neurol Clin Pract. 2017; 7:531–533. doi: 10.1212/CPJ.0000000000000401Google Scholar7. Sennström M, Rova K, Hellgren M, Hjertberg R, Nord E, Thurn L, Lindqvist PG. Thromboembolism and in vitro fertilization - a systematic review.Acta Obstet Gynecol Scand. 2017; 96:1045–1052. doi: 10.1111/aogs.13147Google Scholar8. Siddhartha N, Reddy NS, Pandurangi M, Tamizharasi M, Radha V, Kanimozhi K. Correlation of serum estradiol level on the day of ovulation trigger with the reproductive outcome of intracytoplasmic sperm injection.J Hum Reprod Sci. 2016; 9:23–27. doi: 10.4103/0974-1208.178631Google Scholar9. Gurunath S, Vinekar S, Biliangady R. Assisted reproductive techniques in a patient with history of venous thromboembolism: a case report and review of literature.J Hum Reprod Sci. 2018; 11:193–197. doi: 10.4103/jhrs.JHRS_58_17Google Scholar10. Kumar P, Sait SF, Sharma A, Kumar M. Ovarian hyperstimulation syndrome.J Hum Reprod Sci. 2011; 4:70–75. doi: 10.4103/0974-1208.86080Google Scholar Previous Back to top Next FiguresReferencesRelatedDetails September 2021Vol 52, Issue 9Article InformationMetrics Download: 170 © 2021 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.121.035962PMID: 34348473 Originally publishedAugust 5, 2021 KeywordspregnancywomeninfertilityestrogensthrombophiliaPDF download SubjectsCerebrovascular Disease/Stroke

Vitamin D deficiency, if left untreated, is associated with bone disorders, cardiovascular damage, and an increased risk of ischemic stroke. While there are various nutritional options for the natural intake of vitamin D, we hope to elucidate the potential mechanisms dietary vitamin D may play in hemorrhagic stroke pathology. This scoping review outlines findings from studies relevant to the biochemical activity of vitamin D, the impact of vitamin D deficiency on hemorrhagic stroke outcomes, and the potential benefit of nutritional vitamin D on hemorrhagic stroke outcomes. Here, we analyze the relevant factors that can lead to vitamin D deficiency, and subsequently, a higher risk of hemorrhagic stroke incidence with worsened subsequent outcomes. The neuroprotective mechanisms through which vitamin D works to attenuate hemorrhagic stroke onset and post-stroke outcomes have not yet been thoroughly examined. However, researchers have proposed several potential protective mechanisms, including reduction of blood brain barrier disturbance by inhibiting the production of reactive oxygen species, mitigation of inflammation through a reduction of levels of proinflammatory cytokines, and prevention of cerebral vasospasm and delayed cerebral ischemia following subarachnoid hemorrhage and intracerebral hemorrhage. While more research is needed and there are limitations to vitamin D supplementation, vitamin D as a whole may play a significant role in the dynamics of hemorrhagic stroke. Further research should focus on expanding our understanding of the neuroprotective capacity and mechanisms of vitamin D, as well as how vitamin D supplementation could serve as an effective course of treatment of hemorrhagic strokes.

The spiny mouse (Acomys species ) has emerged as an exciting research organism due to its remarkable ability to undergo scarless regeneration of skin wounds and ear punches. Excitingly, Acomys species demonstrate scar-free healing in a wide-range of tissues beyond the skin. In this perspective article, we discuss published findings from a variety of tissues to highlight how this emerging research organism could shed light on numerous clinically relevant human diseases. We also discuss the challenges of working with this emerging research organism and suggest strategies for future Acomys -inspired research.

Soluble receptors are widely understood to be freestanding moieties formed via cleavage from their membrane-bound counterparts. They have unique structures, are found among various receptor families, and have intriguing mechanisms of generation and release. Soluble receptors' ability to exhibit pleiotropic action by receptor modulation or by exhibiting a dual role in cytoprotection and neuroinflammation is concentration dependent and has continually mystified researchers. Here, we have compiled findings from preclinical and clinical studies to provide insights into the role of soluble/decoy receptors, focusing on the soluble cluster of differentiation 36, the soluble cluster of differentiation 163, and soluble lipoprotein-related protein 1 (sCD36, sCD163, and sLRP1, respectively) and the functions they could likely serve in the management of stroke, as they would notably regulate the bioavailability of the hemoglobin and heme after red blood cell lysis. The key roles that these soluble receptors play in inflammation, oxidative stress, and the related pharmacotherapeutic potential in improving stroke outcomes are described. The precise pleiotropic physiological functions of soluble receptors remain unclear, and further scientific investigation/validation is required to establish their respective role in diagnosis and therapy.