Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations From the SNACC Research Committee.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement.

Propranolol protects cerebral autoregulation and reduces hippocampal neuronal cell death through inhibition of interleukin-6 upregulation after traumatic brain injury in pigs.

Background: Traumatic brain injury (TBI) is associated with reduced cerebral blood flow and impaired autoregulation after TBI, which may lead to poor outcome. Clinical evidence has implicated neurological injuries and associated neuroinflammation as causes of cardiac dysfunction. Studies on newborn pigs show an association of elevated catecholamines with a sex-dependent impairment of cerebral autoregulation after TBI.

Cerebral Perfusion Pressure Directed-Therapy Modulates Cardiac Dysfunction After Traumatic Brain Injury to Influence Cerebral Autoregulation in Pigs.

Background: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with cerebral ischemia, impaired cerebral autoregulation, and poor outcomes. Normalization of CPP and limitation of cerebral autoregulation impairment is a key therapeutic goal.

Translational approach towards determining the role of cerebral autoregulation in outcome after traumatic brain injury.

Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits.

Improving Understanding and Outcomes of Traumatic Brain Injury Using Bidirectional Translational Research.

Recent clinical trials in traumatic brain injury (TBI) have failed to demonstrate therapeutic effects even when there appears to be good evidence for efficacy in one or more appropriate pre-clinical models. While existing animal models mimic the injury, difficulties in translating promising therapeutics are exacerbated by the lack of alignment of discrete measures of the underlying injury pathology between the animal models and human subjects. To address this mismatch, we have incorporated reverse translation of bedside experience to inform pre-clinical studies in a large animal (pig) model of TBI that mirror practical clinical assessments.

Inhaled nitric oxide protects cerebral autoregulation through prevention of impairment of ATP and calcium sensitive K channel mediated cerebrovasodilation after traumatic brain injury.

Hypotension and low cerebral perfusion pressure are associated with low cerebral blood flow, cerebral ischemia, and poor outcomes after traumatic brain injury (TBI). Cerebral autoregulation is impaired after TBI, contributing to poor outcome. In prior studies, ERK mitogen activated protein kinase (MAPK) and ET-1 had been observed to be upregulated and contribute to impairment of cerebral autoregulation and histopathology after fluid percussion brain injury (FPI).

Inhaled Nitric Oxide Protects Cerebral Autoregulation and Reduces Hippocampal Necrosis After Traumatic Brain Injury Through Inhibition of ET-1, ERK MAPK and IL-6 Upregulation in Pigs.

Objective: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Extracellular signal-related kinase (ERK) mitogen activated protein kinase (MAPK) and ET-1 are upregulated and contribute to impairment of cerebral autoregulation and histopathology after porcine fluid percussion brain injury (FPI).

Inhaled Nitric Oxide Protects Cerebral Autoregulation and Reduces Hippocampal Neuronal Cell Necrosis after Traumatic Brain Injury in Newborn and Juvenile Pigs.

Traumatic brain injury (TBI) contributes to morbidity in children, and boys are disproportionately represented. Cerebral blood flow (CBF) is reduced and autoregulation is impaired after TBI, contributing to poor outcome. Cerebral perfusion pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP).

Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude.

Drug delivery by nanocarriers (NCs) has long been stymied by dominant liver uptake and limited target organ deposition, even when NCs are targeted using affinity moieties. Here we report a universal solution: red blood cell (RBC)-hitchhiking (RH), in which NCs adsorbed onto the RBCs transfer from RBCs to the first organ downstream of the intravascular injection. RH improves delivery for a wide range of NCs and even viral vectors.

Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET-1 and JNK.

The sole FDA-approved drug treatment for ischemic stroke is tissue-type plasminogen activator (tPA). However, upregulation of JNK mitogen-activated protein kinase (MAPK) and endothelin 1 (ET-1) by tPA after stroke contributes to impaired cerebrovascular autoregulation. Wild-type (wt) tPA can bind to the lipoprotein-related receptor (LRP), which mediates vasodilation, or NMDA receptors (NMDA-Rs), exacerbating vasoconstriction.

tPA variant tPA-A Prevents impairment of cerebral autoregulation and necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET-1.

Tissue-type plasminogen activator (tPA) is neurotoxic and exacerbates uncoupling of cerebral blood flow (CBF) and metabolism after stroke, yet it remains the sole FDA-approved drug for treatment of ischemic stroke. Upregulation of c-Jun-terminal kinase (JNK) after stroke contributes to tPA-mediated impairment of autoregulation, but the role of endothelin-1 (ET-1) is unknown. Based on the Glasgow Coma Scale, impaired autoregulation is linked to adverse outcomes after TBI, but correlation with hippocampal histopathology after stroke has not been established.

Dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of ERK MAPK in juvenile pigs.

Traumatic brain injury (TBI) contributes to morbidity in children, and more boys experience TBI. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP).

K channel impairment determines sex and age differences in epinephrine-mediated outcomes after brain injury.

Traumatic brain injury (TBI) is the leading cause of injury-related death in children, with boys and children under 4 years having particularly poor outcomes. Activation of ATP- and calcium-sensitive (K and K ) channels produces cerebrovasodilation and contributes to autoregulation, both of which are impaired after TBI, contributing to poor outcomes. Upregulation of the c-Jun-terminal kinase (JNK) isoform of mitogen-activated protein kinase produces K channel function impairment after CNS injury.

Sex and age differences in phenylephrine mechanisms and outcomes after piglet brain injury.

BackgroundTraumatic brain injury (TBI) is the leading cause of injury-related death in children, with boys and children under 4 years of age having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. In prior studies on newborn pigs, phenylephrine (Phe) preferentially protected cerebral autoregulation in female but not in male subjects after TBI.

Sex and Age Differences in Epinephrine Mechanisms and Outcomes after Brain Injury.

Traumatic brain injury (TBI) is the leading cause of injury-related death in children, with boys and children <4 years of age having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. Cerebral perfusion pressure can be normalized by use of vasoactive agents.

Cerebral Blood Flow Autoregulation and Dysautoregulation.

This article provides a review of cerebral autoregulation, particularly as it relates to the clinician scientist experienced in neuroscience in anesthesia and critical care. Topics covered are biological mechanisms; methods used for assessment of autoregulation; effects of anesthetics; role in control of cerebral hemodynamics in health and disease; and emerging areas, such as role of age and sex in contribution to dysautoregulation. Emphasis is placed on bidirectional translational research wherein the clinical informs the study design of basic science studies, which, in turn, informs the clinical to result in development of improved therapies for treatment of central nervous system conditions.

Tissue-Type Plasminogen Activator-A296-299 Prevents Impairment of Cerebral Autoregulation After Stroke Through Lipoprotein-Related Receptor-Dependent Increase in cAMP and p38.

Background And Purpose: The sole Food and Drug Administration-approved treatment for stroke is tissue-type plasminogen activator (tPA), but its brief therapeutic window and complications of treatment constrain its use. One limitation may be its potential to exacerbate impairment of cerebral autoregulation after stroke. Vasodilation is maintained by elevations in cAMP.

Preferential Protection of Cerebral Autoregulation and Reduction of Hippocampal Necrosis With Norepinephrine After Traumatic Brain Injury in Female Piglets.

Objectives: Traumatic brain injury contributes to morbidity in children and boys is disproportionately represented. Cerebral autoregulation is impaired after traumatic brain injury, contributing to poor outcome. Cerebral perfusion pressure is often normalized by the use of vasopressors to increase mean arterial pressure.

Norepinephrine Protects Cerebral Autoregulation and Reduces Hippocampal Necrosis after Traumatic Brain Injury via Blockade of ERK MAPK and IL-6 in Juvenile Pigs.

Traumatic brain injury (TBI) contributes to morbidity in children, and boys are disproportionately represented. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral perfusion pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP).

Microparticles Impair Hypotensive Cerebrovasodilation and Cause Hippocampal Neuronal Cell Injury after Traumatic Brain Injury.

Endothelin-1 (ET-1), tissue plasminogen activator (tPA), and extracellular signal-regulated kinases-mitogen activated protein kinase (ERK-MAPK) are mediators of impaired cerebral hemodynamics after fluid percussion brain injury (FPI) in piglets. Microparticles (MPs) are released into the circulation from a variety of cells during stress, are pro-thrombotic and pro-inflammatory, and may be lysed with polyethylene glycol telomere B (PEG-TB). We hypothesized that MPs released after traumatic brain injury impair hypotensive cerebrovasodilation and that PEG-TB protects the vascular response via MP lysis, and we investigated the relationship between MPs, tPA, ET-1, and ERK-MAPK in that process.