Mechanistic and therapeutic relationships of traumatic brain injury and γ-amino-butyric acid (GABA).

Traumatic brain injury (TBI) is a highly prevalent medical condition for which no medications specific for the prophylaxis or treatment of the condition as a whole exist. The spectrum of symptoms includes coma, headache, seizures, cognitive impairment, depression, and anxiety. Although it has been known for years that the inhibitory neurotransmitter γ-amino-butyric acid (GABA) is involved in TBI, no novel therapeutics based upon this mechanism have been introduced into clinical practice.

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

Objective: To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).

Methods: We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness.

Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.

The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers).

Loss of consciousness at onset of aneurysmal subarachnoid hemorrhage in good-grade patients.

Loss of consciousness (LOC) at presentation with aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury and poor functional outcome. The impact of LOC on the clinical course after aSAH deserves further exploration. A retrospective analysis of 149 aSAH patients who were prospectively enrolled in the Cerebral Aneurysm Renin Angiotensin Study (CARAS) between 2012 and 2015 was performed.

Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI-1 for the regulation of tissue plasminogen activator is considered an important therapeutic target for aSAH.

Methods: Six SNPs in the SERPINE1 gene (in order of rs2227631, rs1799889, rs6092, rs6090, rs2227684, rs7242) were investigated.

Association of a Functional Polymorphism in the Gene with Inflammatory Response Mediators and Neuropathic Pain after Spinal Cord Injury.

The alpha 7 nicotinic acetylcholine receptor, α7 nAChR, plays a central role in regulating inflammatory responses. Previous studies showed that pharmacological inhibitors of α7nAChR have a pro-inflammatory effect, increasing the circulating levels of cytokines such as tumor necrosis factor alpha (TNFα). This study focused on how genetic polymorphisms of the partially duplicated α7nAChR gene (), which is highly expressed in peripheral blood cells, contribute to functional outcome after spinal cord injury (SCI).

Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus.

Bhlhe40 is a transcription factor that is highly expressed in the hippocampus; however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO) to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity in the hippocampus. Bhlhe40 KO CA1 neurons had increased miniature excitatory post-synaptic current amplitude and decreased inhibitory post-synaptic current amplitude, indicating CA1 neuronal hyperexcitability.

PHASES score applied to a prospective cohort of aneurysmal subarachnoid hemorrhage patients.

The treatment of unruptured intracranial aneurysms remains controversial. The PHASES score was developed to predict the 5-year risk of aneurysm rupture. We have assigned PHASES scores to a cohort of aneurysmal subarachnoid hemorrhage (aSAH) patients to assess the distribution of scores and its ability to predict outcome.

The role of endothelial nitric oxide synthase -786 T/C polymorphism in cardiac instability following aneurysmal subarachnoid hemorrhage.

Introduction: Cardiac abnormalities are observed frequently after aneurysmal subarachnoid hemorrhage (aSAH). A subset of aSAH patients develops neurogenic cardiomyopathy, likely induced by catecholamine excess. Genetic polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been linked to decreased nitric oxide (NO) levels, coronary artery spasm, and myocardial infarction.

Association of cystathionine beta-synthase polymorphisms and aneurysmal subarachnoid hemorrhage.

OBJECTIVE Cystathionine β-synthase (CBS) is involved in homocysteine and hydrogen sulfide (HS) metabolism. Both products have been implicated in the pathophysiology of cerebrovascular diseases. The impact of CBS polymorphisms on aneurysmal subarachnoid hemorrhage (aSAH) and its clinical sequelae is poorly understood.

Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage.

Background: Genetic variations of the serine proteinase inhibitor family E member 1 (SERPINE1) gene, which encodes plasminogen activator inhibitor 1, correlate with serum levels of its product and are associated with thrombophilia and coronary atherosclerosis. Various SERPINE1 ;gene polymorphisms have been identified. However, only the functional 5G/4G polymorphism has been assessed in the context of aneurysmal subarachnoid hemorrhage (aSAH).

Associations between endothelin polymorphisms and aneurysmal subarachnoid hemorrhage, clinical vasospasm, delayed cerebral ischemia, and functional outcome.

OBJECTIVE Endothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated. METHODS Blood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation.

Functional human promoter polymorphism and variation of mental processing speed in older adults.

We investigated the role of a single nucleotide polymorphism rs3764030 (G>A) within the human promoter in mental processing speed in healthy, cognitively intact, older adults. DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.

Endothelin polymorphisms as a risk factor for cerebral aneurysm rebleeding following aneurysmal subarachnoid hemorrhage.

Background: Aneurysm rebleeding following presentation with aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor functional outcome. While a substantial genetic contribution to aneurysm formation and rupture is known, the genetic influence on the risk of rebleeding is poorly understood.

Objective: To evaluate the role of common endothelin polymorphisms in aneurysm rebleeding.

Associations of Endothelin Polymorphisms and Aneurysm Size at Time of Rupture.

Background And Purpose: Aneurysm size is an important risk factor for aneurysm rupture. The pathophysiologic mechanisms underlying aneurysm growth remain poorly understood. Endothelin signaling is critical for cerebrovascular blood flow regulation.

Endothelial Nitric Oxide Synthase Polymorphism Is Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage.

Background And Purpose: Nitric oxide is critical in the regulation of cerebral blood flow and smooth muscle proliferation. It is synthesized by 3 nitric oxide synthase (NOS) isoforms: neuronal, inducible, and endothelial NOS (eNOS). Aneurysmal subarachnoid hemorrhage (aSAH) causes endothelial dysfunction that, in turn, contributes to pathophysiologic processes surrounding aSAH.

Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Background And Objective: The high-mobility group box 1 (HMGB1) protein is a eukaryotic, ubiquitously expressed protein that serves as a biomarker for various diseases and is involved in the promotion of a proinflammatory response to cell injury. In aneurysmal subarachnoid hemorrhage (aSAH), increased HMGB1 levels have been linked to poor outcome and an increased risk for cerebral vasospasm. The role of HMGB1 polymorphisms in aSAH has not been previously investigated.

Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage.

OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients and controls at 2 academic centers in the United States.

Ryanodine Receptor 1 Polymorphism Is Not Associated with Aneurysmal Subarachnoid Hemorrhage or its Clinical Sequelae.

Objective: The pathophysiologic mechanisms underlying cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understand. Ryanodine receptors (RYR) are intracellular calcium channels involved in the regulation of vascular smooth muscle cells and cerebrovascular tone and diameter. Previous work reported an association between an RYR polymorphism and cerebral vasospasm.

Predictors of Shunt Insertion in Aneurysmal Subarachnoid Hemorrhage.

Objective: Hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), requiring permanent cerebrospinal fluid (CSF) diversion in up to two thirds of patients. Factors that predict permanent CSF diversion are not well established.

Methods: An exploratory analysis of 149 patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study was performed in an effort to identify factors predictive of permanent CSF diversion after aSAH; only the 135 patients surviving the initial hospitalization were included in the present study.

Associations of renin-angiotensin system genetic polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage.

OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin Angiotensin System (CARAS) study prospectively evaluated associations of common RAS polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients at 2 academic centers in the United States.

Association of nosocomial infections with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

OBJECTIVE Delayed cerebral ischemia (DCI) is a recognized complication of aneurysmal subarachnoid hemorrhage (aSAH) that contributes to poor outcome. This study seeks to determine the effect of nosocomial infection on the incidence of DCI and patient outcome. METHODS An exploratory analysis was performed on 156 patients with aSAH enrolled in the Cerebral Aneurysm Renin Angiotensin System study.

Alpha-linolenic acid: an omega-3 fatty acid with neuroprotective properties-ready for use in the stroke clinic?

Alpha-linolenic acid (ALA) is plant-based essential omega-3 polyunsaturated fatty acids that must be obtained through the diet. This could explain in part why the severe deficiency in omega-3 intake pointed by numerous epidemiologic studies may increase the brain's vulnerability representing an important risk factor in the development and/or deterioration of certain cardio- and neuropathologies. The roles of ALA in neurological disorders remain unclear, especially in stroke that is a leading cause of death.