endothelin-1 and Brain-Injuries--Traumatic

To investigate the effects of probiotics combined with early enteral nutrition on levels of endothelin-1 (ET-1), C-reactive protein (CRP), and inflammatory factors, and on the prognosis of patients with severe traumatic brain injury (TBI).. We enrolled 76 adults with severe TBI. The patients were divided randomly into two equal groups administered enteral nutrition with and without probiotics, respectively. Demographic and clinical data including age, sex, Glasgow Coma Scale score, Sequential Organ Failure Score, Acute Physiology, Chronic Health Score, hospitalization, mortality, and infections were recorded.. Serum levels of inflammatory factors gradually decreased with increasing treatment time in both groups. However, ET-1 at 15 days, and interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and CRP at 7 and 15 days decreased significantly more in the combined treatment group. Hospitalization duration and pulmonary infection rates were also significantly reduced in the combined compared with the enteral nutrition alone group. GCS scores at 15 days were significantly lower in the combined compared with the enteral nutrition group.. Probiotics combined with early enteral nutrition could reduce serum levels of ET-1, CRP, and IL-6, IL-10, and TNF-α, and could thus improve the recovery of patients with severe TBI.

Topics: Adult; Brain Injuries, Traumatic; C-Reactive Protein; Endothelin-1; Enteral Nutrition; Humans; Probiotics; Prognosis

In the adult brain, sonic hedgehog acts on cerebral microvascular endothelial cells to stabilize the blood-brain barrier. The expression of sonic hedgehog by astrocytes is altered during brain injury, and this change has been shown to affect permeability of blood-brain barrier. However, much remains unknown about the regulation of astrocytic sonic hedgehog production. Our results showed that endothelin-1 reduced sonic hedgehog mRNA expression and extracellular protein release in mouse cerebral cultured astrocytes, but had no effect in bEnd.3, a mouse brain microvascular endothelial-derived cell line. The effect of endothelin-1 on astrocyte sonic hedgehog expression was suppressed by an ET

Topics: Animals; Astrocytes; Blood-Brain Barrier; Brain Injuries, Traumatic; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Endothelin-1; Hedgehog Proteins; Male; Mice; Oligopeptides; Piperidines; Receptor, Endothelin B; Veratrum Alkaloids

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). Recent studies show that inhaled nitric oxide (iNO) prevents impairment of cerebral autoregulation and histopathology after FPI in pigs. Unrelated studies indicated an association between ERK and increased IL-6 after FPI. However, the role of IL-6 in central nervous system (CNS) pathology is not well understood. We investigated whether iNO protects autoregulation and limits histopathology after FPI in pigs due to modulation of brain injury associated upregulation of ET-1, ERK MAPK, and IL-6.. Lateral FPI was produced in anesthetized pigs equipped with a closed cranial window and iNO administered at 30 min or 2 h post injury.. CSF ET-1, ERK MAPK, and IL-6 were increased by FPI, but release was blocked by iNO administered at 30 min or 2 h after TBI. The IL-6 antagonist LMT-28 prevented impairment of cerebral autoregulation and hippocampal CA1 and CA3 neuronal necrosis after FPI. Papaverine induced dilation was unchanged by FPI and LMT-28. Protection lasted for at least 2 h after iNO administration was stopped.. These data indicate that iNO protects cerebral autoregulation and reduces hippocampal necrosis after traumatic brain injury through inhibition of ET-1, ERK MAPK, and IL-6 upregulation in pigs.

Topics: Administration, Inhalation; Animals; Animals, Newborn; Brain Injuries, Traumatic; Disease Models, Animal; Endothelin-1; Extracellular Signal-Regulated MAP Kinases; Female; Hippocampus; Homeostasis; Interleukin-6; Male; Necrosis; Nitric Oxide; Oxazolidinones; Papaverine; Protein Synthesis Inhibitors; Signal Transduction; Swine; Up-Regulation; Vasodilator Agents

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). Activation of ATP and Calcium sensitive (Katp and Kca) channels produce cerebrovasodilation and contribute to autoregulation, both impaired after TBI. Upregulation of ERK MAPK and endothelin-1 (ET-1) produces K channel function impairment after CNS injury. Inhaled nitric oxide (iNO) has recently been observed to prevent impairment of cerebral autoregulation and hippocampal CA1 and CA3 neuronal cell necrosis after FPI via block of upregulation of ERK MAPK and ET-1. We presently investigated whether iNO prevented impairment of Katp and Kca-mediated cerebrovasodilation after FPI in pigs equipped with a closed cranial window. Results show that pial artery dilation in response to the Katp agonist cromakalim, the Kca agonist NS1619, PGE2 and the NO releaser sodium nitroprusside (SNP) were blocked by FPI, but such impairment was prevented by iNO administered at 2 h post injury. Protection lasted for at least 1 h after iNO administration was stopped. Using vasodilaton as an index of function, these data indicate that iNO prevents impairment of cerebral autoregulation and limits histopathology after TBI through protection of K channel function via blockade of ERK MAPK and ET-1.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain Injuries, Traumatic; Calcium; Calcium Channels; Cerebrovascular Circulation; Endothelin-1; Extracellular Signal-Regulated MAP Kinases; Female; Homeostasis; Male; Nitric Oxide; Potassium Channels, Calcium-Activated; Swine; Vasodilation; Vasodilator Agents

Topics: Brain Injuries; Brain Injuries, Traumatic; Child; Endothelin-1; Humans

Many studies have reported that lutein may exert its biological activities, including anti‑inflammation, anti‑oxidase and anti‑apoptosis, through effects on reactive oxygen species (ROS). Thus, lutein may prevent the damaging activities of ROS in cells. The current study investigated the effect of lutein against severe traumatic brain injury (STBI) and examined the mechanism of this protective effect. Sprague‑Dawley rats were randomly divided into 5 groups: Control group, STBI model group, 40 mg/kg lutein‑treated group, 80 mg/kg lutein‑treated group and 160 mg/kg lutein‑treated group. In this study, lutein protects against STBI, suppressed, interleukin (IL)‑1β, IL‑6 and monocyte chemoattractant protein‑1 expression, reduced serum ROS levels, and reduced superoxide dismutase and glutathione peroxidase activities in STBI rats. Treatment with lutein effectively downregulated the expression of NF‑κB p65 and cyclooxygenase‑2, intercellular adhesion molecule (ICAM)‑1 protein, and upregulated nuclear factor erythroid 2 like 2 (Nrf‑2) and endothelin‑1 protein levels in STBI rats. These findings demonstrated that lutein protects against STBI, has anti‑inflammation and antioxidative effects and alters ICAM‑1/Nrf‑2 expression, which may be a novel therapeutic for STBI the clinic.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain Injuries, Traumatic; Contusions; Cyclooxygenase 2; Endothelin-1; Intercellular Adhesion Molecule-1; Lutein; Male; Motor Activity; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Protective Agents; Rats, Sprague-Dawley; Reactive Oxygen Species