.

Aneurysmal subarachnoid hemorrhage (aSAH) may be associated with cerebral vasospasm, which can lead to delayed cerebral ischemia, infarction, and worsened functional outcomes. The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Secondary ischemic injury in SAH is associated with increased extracellular glutamate, which can overactivate NMDA receptors (NMDARs), thereby triggering NMDAR-mediated cellular damage.

Effects of Amyloid Beta (Aβ) Oligomers on Blood-Brain Barrier Using a 3D Microfluidic Vasculature-on-a-Chip Model.

The disruption of the blood-brain barrier (BBB) in Alzheimer's Disease (AD) is largely influenced by amyloid beta (Aβ). In this study, we developed a high-throughput microfluidic BBB model devoid of a physical membrane, featuring endothelial cells interacting with an extracellular matrix (ECM). This paper focuses on the impact of varying concentrations of Aβ oligomers on BBB dysfunction by treating them in the luminal.

RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC).

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work.

Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

Background: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking.

Objective: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI.

Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III).

Background: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke.

Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

Background: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction.

Optimization of a translational murine model of closed-head traumatic brain injury.

Traumatic brain injury (TBI) from closed-head trauma is a leading cause of disability, with limited effective interventions. Many TBI models impact brain parenchyma directly, and are limited by the fact that these forces do not recapitulate clinically relevant closed head injury. However, applying clinically relevant injury mechanics to the intact skull may lead to variability and as a result, preclinical modeling TBI remains a challenge.

A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke.

Stroke remains a leading cause of death and disability in the US, and time-limited reperfusion strategies remain the only approved treatment options. To address this unmet clinical need, we conducted a phase II randomized clinical trial to determine whether intravenous infusion of banked, non-HLA matched unrelated donor umbilical cord blood (UCB) improved functional outcome after stroke. Participants were randomized 2:1 to UCB or placebo within strata of National Institutes of Health Stroke Scale Score (NIHSS) and study center.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

Objective: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI).

Design: Retrospective cohort study with prospectively collected data.

Setting: Eighteen Level-1 Trauma Centers, United States.

Cortical spheroid on perfusable microvascular network in a microfluidic device.

Human induced pluripotent stem cell (hiPSC)-derived brain spheroids can recapitulate the complex cytoarchitecture of the brain, as well as the genetic/epigenetic footprint of human brain development. However, hiPSC-derived 3D models such as spheroid and organoids does not have a perfusable microvascular network, which plays a vital role in maintaining homeostasis in vivo. With the critical balance of positive and negative angiogenic modulators, 3D microvascular network can be achieved by angiogenesis.

ApoE Mimetic Peptides as Therapy for Traumatic Brain Injury.

The lack of targeted therapies for traumatic brain injury (TBI) remains a compelling clinical unmet need. Although knowledge of the pathophysiologic cascades involved in TBI has expanded rapidly, the development of novel pharmacological therapies has remained largely stagnant. Difficulties in creating animal models that recapitulate the different facets of clinical TBI pathology and flaws in the design of clinical trials have contributed to the ongoing failures in neuroprotective drug development.

Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor.

NP10679 is a context-dependent and subunit-selective negative allosteric modulator of N-methyl-d-aspartate (NMDA) receptors. It is a more potent inhibitor of GluN2B-containing NMDA receptors at the acidic levels of extracellular pH (eg, 6.9) found in the penumbral regions associated with cerebral ischemia than at physiological pH.

Utilization and Outcomes of Extracorporeal Membrane Oxygenation Following Traumatic Brain Injury in the United States.

Describe contemporary ECMO utilization patterns among patients with traumatic brain injury (TBI) and examine clinical outcomes among TBI patients requiring ECMO. Retrospective cohort study. Premier Healthcare Database (PHD) between January 2016 to June 2020.

Surgical Considerations to Improve Recovery in Acute Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) can be a devastating and costly event for individuals, their families, and the health system as a whole. Prognosis is heavily dependent on the physical extent of the injury and the severity of neurological dysfunction. If not treated urgently, individuals can suffer exacerbated secondary injury cascades that may increase tissue injury and limit recovery.

Effect of Acute Physical Interventions on Pathophysiology and Recovery After Spinal Cord Injury: A Comprehensive Review of the Literature.

Physical rehabilitation is essential for enhancing recovery in individuals with spinal cord injury (SCI); however, aside from early surgical intervention and hemodynamic management, there are no proven interventions for promoting recovery in the acute phase. In general, early rehabilitation is considered beneficial, but optimal parameters and potential contraindications for implementing rehabilitation at very early time points are unclear. Moreover, clinical trials to date are limited to studies initiating rehabilitation 2 weeks after injury and later.

Analysis of Prescriptions for Dual Antiplatelet Therapy After Acute Ischemic Stroke.

Importance: After the publication of the CHANCE (Clopidogrel in High Risk Patients With Acute Nondisabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke) clinical trials, the American Heart Association/American Stroke Association (AHA/ASA) issued a new class 1, level of evidence A, recommendation for dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) for secondary prevention in patients with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤3). The extent to which variations in DAPT prescribing patterns remain and the extent to which practice patterns in the US are consistent with evidence-based guidelines are unknown.

Objective: To evaluate the discharge DAPT prescribing patterns after publication of the new AHA/ASA guidelines and assess the extent of hospital-level variation in the use of DAPT for secondary prevention in patients with minor stroke (NIHSS score ≤3), as indicated by guidelines, and in patients with nonminor stroke (NIHSS score >3), for whom the risks and benefits of DAPT have not been fully established.

Safe performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with HIV infection.

Background: Patients with HIV (PHIV) are living longer with the adoption of anti-retroviral therapy. As such, more patients are presenting with advanced cancer diagnoses, including peritoneal surface malignancies. The objective of this study was to assess the safety of CRS/HIPEC in this cohort of patients.

Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury.

The treatment of traumatic brain injury (TBI) in military populations is hindered by underreporting and underdiagnosis. Clinical symptoms and outcomes may be mitigated with an effective pre-injury prophylaxis. This study evaluates whether CN-105, a 5-amino acid apolipoprotein E (ApoE) mimetic peptide previously shown to modify the post-traumatic neuroinflammatory response, would maintain its neuroprotective effects if administered prior to closed-head injury in a clinically relevant murine model.

An Exploratory Analysis of Biomarkers of Perihematomal Edema in the CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.

Objective: To identify biomarkers with potential to indicate severity of perihematomal edema and secondary tissue injury after intracerebral hemorrhage (ICH), and which could be used as surrogate markers in future clinical trials for novel ICH therapeutics.

Materials And Methods: This exploratory cohort study compared trends in neuroinflammatory biomarker levels in 18 consecutively enrolled patients with acute supratentorial ICH and 16 patients treated with the investigational neuroprotective therapy CN-105 to identify a panel of 10 biomarkers. Biomarker levels over five days post-hemorrhage were then compared with edema volumes in a larger sample of patients treated with CN-105.