Neurocritical care
-
Review
The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.
When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. ⋯ Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.
-
Randomized Controlled Trial
A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage.
Epoxyeicosatrienoates (EETs) are endogenous regulators of neuroinflammation and cerebral blood flow. Their metabolism to dihydroxyeicosatrienoates (DHETs) is catalyzed by soluble epoxide hydrolase (sEH). After subarachnoid hemorrhage (SAH), EETs' pathway amplification may be a therapeutic target for the prevention of delayed cerebral ischemia (DCI). We conducted a double-blind, placebo-controlled, phase Ib randomized trial of GSK2256294, a pharmacologic inhibitor of sEH, to evaluate the safety profile and to assess biomarkers of neurovascular inflammation in patients with aneurysmal SAH. ⋯ ClinicalTrials.gov: NCT03318783.
-
Review
Microglia Modulate Cortical Spreading Depolarizations After Ischemic Stroke: A Narrative Review.
Cortical spreading depolarizations (CSDs) are characterized by waves of diminished electroencephalography activity that propagate across the cortex with subsequent loss of ionic homeostasis. CSDs have been found in many pathological conditions, including migraine, traumatic brain injury, and ischemic stroke. Because of CSD-associated ionic and metabolic disturbances at the peri-infarct area after ischemic stroke, it is thought that CSDs exacerbate tissue infarction and worsen clinical outcomes. ⋯ Recent studies demonstrated that microglia play a critical role in CSD initiation and propagation. In this article, we discuss the significance of CSD in the setting of ischemic stroke and how microglia may modulate peri-infarct CSDs, also known as iso-electric depolarizations. Finally, we discuss the significance of microglial Ca2+ and how it might be used as a potential therapeutic target for patients with ischemic stroke.
-
Review
Impact of Cerebral Autoregulation Monitoring in Cerebrovascular Disease: A Systematic Review.
Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This process is disrupted consequent to various neurologic pathologic processes, which may result in worsening neurologic outcomes. Herein, we aim to highlight evidence describing CA changes and the impact of CA monitoring in patients with cerebrovascular disease, including ischemic stroke, intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (aSAH). ⋯ This systematic review highlights the available evidence for CA disruption during cerebrovascular diseases and its possible association with long-term neurological outcome. CA may be disrupted even before acute stroke in patients with untreated chronic hypertension. Monitoring CA may help in establishing individualized management targets in patients with cerebrovascular disease.
-
Randomized Controlled Trial
Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage.
This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored. ⋯ We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood-brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.