Update on Strategies to Reduce Early Brain Injury after Subarachnoid Hemorrhage.

Purpose Of Review: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets.

Mitochondrial-targeted therapies in traumatic brain injury: From bench to bedside.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, with limited effective therapeutic options currently available. Recent research has highlighted the pivotal role of mitochondrial dysfunction in the pathophysiology of TBI, making mitochondria an attractive target for therapeutic intervention. This review comprehensively examines advancements in mitochondrial-targeted therapies for TBI, bridging the gap from basic research to clinical applications.

Metabolomic and lipidomic pathways in aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) results in a complex systemic response that is critical to the pathophysiology of late complications and has important effects on outcomes. Omics techniques have expanded our investigational scope and depth into this phenomenon. In particular, metabolomics-the study of small molecules, such as blood products, carbohydrates, amino acids, and lipids-can provide a snapshot of dynamic subcellular processes and thus broaden our understanding of molecular-level pathologic changes that lead to the systemic response after aSAH.

Trajectory clustering of immune cells and its association with clinical outcomes after aneurysmal subarachnoid hemorrhage.

Background And Purpose: The immune response following aneurysmal subarachnoid hemorrhage (aSAH) can exacerbate secondary brain injury and impact clinical outcomes. As the immune response after aSAH is a dynamic process, we aim to track and characterize immune cell trajectories over time to identify patterns associated with various clinical outcomes.

Methods: In this retrospective single-center study of patients with aSAH, we analyzed immune cell count trajectories, including neutrophil, monocyte, and lymphocyte counts, collected from day 1 to day 14.

Aromatase, testosterone, TMPRSS2: determinants of COVID-19 severity.

Background: Male sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens.

Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.

Background: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI.

A systematic review of the timing of therapeutic anticoagulation in adult patients with acute traumatic brain injury: narrative synthesis of observational studies.

Traumatic brain injury (TBI) presents complex management scenarios, particularly in patients requiring anticoagulation for concurrent conditions such as venous thromboembolism (VTE) or atrial fibrillation (AF). A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria encompassed studies assessing the effects of anticoagulation therapy on outcomes such as re-hemorrhage, hematoma expansion, thrombotic events, and hemorrhagic events in TBI patients with subdural hematomas (SDH).

The Effect of Age on Cerebral Vasospasm and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

Background: The association between patient age and cerebral arterial vasospasm (CVS) and delayed cerebral ischemia (DCI) risk following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. This study aims to assess the role of age on aSAH-related complications.

Methods: Single-center retrospective study comprising aSAH patients treated between January 2009 and March 2023.

Racial and Ethnic Differences in Mortality and Functional Outcomes Following Aneurysmal Subarachnoid Hemorrhage.

Background: Ischemic and hemorrhagic stroke incidence tends to be higher among minority racial and ethnic groups. The effect of race and ethnicity following an aneurysmal subarachnoid hemorrhage (aSAH) remains poorly understood. Thus, we aimed to explore the association between race and ethnicity and aSAH outcomes.

Updates of the role of B-cells in ischemic stroke.

Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate a protective effect, which is released step by step and contributes to the repair of neuronal cells through phenotypic changes.

Detection of Acute Brain Injury in Intensive Care Unit Patients on ECMO Support Using Ultra-Low-Field Portable MRI: A Retrospective Analysis Compared to Head CT.

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO).

Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and Its Effects on Acute Ischemic Stroke to Improve Outcomes.

Background: While renin-angiotensin system (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns.

Methods: Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were Acute Ischemic Stroke (AIS) patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment.

A generalizable physiological model for detection of Delayed Cerebral Ischemia using Federated Learning.

Delayed cerebral ischemia (DCI) is a complication seen in patients with subarachnoid hemorrhage stroke. It is a major predictor of poor outcomes and is detected late. Machine learning models are shown to be useful for early detection, however training such models suffers from small sample sizes due to rarity of the condition.

Cerebrovascular Complications Associated With Iatrogenic Fungal Meningitis Following Surgical Procedures in Mexico.

Background: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis.

Role of microRNA-34a in blood-brain barrier permeability and mitochondrial function in ischemic stroke.

Over the past decade, there has been an uptick in the number of studies conducting research on the role of microRNA (miRNA) molecules in stroke. Among these molecules, miR-34a has emerged as a significant player, as its levels have been observed to exhibit a substantial rise following ischemic events. Elevated levels of miR-34a have been found to have multiple effects, including the modulation of inflammatory molecules involved in the post-stroke recovery process, as well as negative effects on the blood-brain barrier (BBB) permeability.

Peripheral eosinophil trends and clinical outcomes after non-traumatic subarachnoid hemorrhage.

Background/objective: Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse outcomes. Changes in the peripheral eosinophil count have been linked to worse clinical outcomes after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical outcomes after SAH.

Leucine-Rich Alpha-2-Glycoprotein 1 is a Systemic Biomarker of Early Brain Injury and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

Background: After subarachnoid hemorrhage (SAH), early brain injury (EBI) and delayed cerebral ischemia (DCI) lead to poor outcomes. Discovery of biomarkers indicative of disease severity and predictive of DCI is important. We tested whether leucine-rich alpha-2-glycoprotein 1 (LRG1) is a marker of severity, DCI, and functional outcomes after SAH.

Systemic inflammatory markers of persistent cerebral edema after aneurysmal subarachnoid hemorrhage.

Background: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE.

Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial.

Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer--acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19.