Functional and Structural Improvement with a Catalytic Carbon Nano-Antioxidant in Experimental Traumatic Brain Injury Complicated by Hypotension and Resuscitation.

Hypotension worsens outcome after all severities of traumatic brain injury (TBI), with loss of cerebral autoregulation being a potential contributor. Previously, we demonstrated that intravenous injection of a high capacity catalytic antioxidant, poly(ethylene)glycol conjugated hydrophilic carbon clusters (PEG-HCCs) rapidly restored cerebral perfusion and acutely restored brain oxidative balance in a TBI model complicated by hemorrhagic hypotension without evidence of toxicity. Here, we tested whether these acute effects translated into behavioral and structural benefit.

Arginase overexpression in neurons and its effect on traumatic brain injury.

Arginine is a semi-essential amino acid which serves as a substrate for nitric oxide (NO) production by nitric oxide synthase (NOS) and a precursor for various metabolites including ornithine, creatine, polyamines, and agmatine. Arginase competes with nitric oxide synthase for substrate arginine to produce orthinine and urea. There is contradictory evidence in the literature on the role of nitric oxide in the pathophysiology of traumatic brain injury (TBI).

Axon initial segment-associated microglia.

Microglia are the brain's resident immune cells and function as the main defense against pathogens or injury. However, in the absence of disease, microglia have other functions in the normal brain. For example, previous studies showed that microglia contribute to circuit refinement and synaptic plasticity in the developing and adult brain, respectively.

Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury.

Injury to the neurovasculature is a feature of brain injury and must be addressed to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after traumatic brain injury (TBI), most notably under conditions of hypotension. We report here that a new class of antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), which are nontoxic carbon particles, rapidly restore CBF in a mild TBI/hypotension/resuscitation rat model when administered during resuscitation--a clinically relevant time point.

Histopathological and behavioral effects of immediate and delayed hemorrhagic shock after mild traumatic brain injury in rats.

The purpose of this study was to investigate the increased susceptibility of the brain, after a controlled mild cortical impact injury, to a secondary ischemic insult. The effects of the duration and the timing of the secondary insult after the initial cortical injury were studied. Rats anesthetized with isoflurane underwent a 3 m/sec, 2.

Neuroprotection with an erythropoietin mimetic peptide (pHBSP) in a model of mild traumatic brain injury complicated by hemorrhagic shock.

Pyroglutamate helix B surface peptide (pHBSP) is an 11 amino acid peptide, designed to interact with a novel cell surface receptor, composed of the classical erythropoietin (EPO) receptor disulfide linked to the beta common receptor. pHBSP has the cytoprotective effects of EPO without stimulating erythropoiesis. Effects on early cerebral hemodynamics and neurological outcome at 2 weeks post-injury were compared in a rat model of mild cortical impact injury (3m/sec, 2.

Improved cerebrovascular function and reduced histological damage with darbepoietin alfa administration after cortical impact injury in rats.

Darbepoetin alfa (darbEpo) is an erythropoietic glycoprotein that activates the erythropoietin receptor. The aim of our study was to determine whether darbEpo is neuroprotective in a cortical impact injury (CII) model and to determine the characteristics of dose response and time window. To better understand the vascular mechanism of darbEpo neuroprotection, the reactivity of cerebral blood flow (CBF) to l-arginine administration was also studied.

Cerebral microdialysis of interleukin (IL)-1beta and IL-6: extraction efficiency and production in the acute phase after severe traumatic brain injury in rats.

Background: As a research tool, cerebral microdialysis might be a useful technique in monitoring the release of cytokines into the extracellular fluid (ECF) following traumatic brain injury (TBI). We established extraction efficiency of Interleukin(IL)-1ss and Interleukin(IL)-6 by an in vitro microdialysis-perfusion system, followed by in vivo determination of the temporal profile of extracellular fluid cytokines after severe TBI in rats.

Materials And Methods: In vitro experiments using a polyether sulfon (PES) microdialysis probe especially developed for recovery of macromolecules such as cytokines, were carried out to establish the extraction efficiency of IL-1ss and IL-6 from artificial cerebrospinal fluid (CSF) with defined IL-1ss and IL-6 concentrations.

Neuroprotection with erythropoietin administration following controlled cortical impact injury in rats.

This study was designed to determine the effect of erythropoietin (Epo) on cerebral blood flow (CBF), nitric oxide (NO) concentration, and neurological outcome after traumatic brain injury. In one experiment, the hemodynamic effects of Epo were determined after controlled cortical impact injury (CCII) by measuring mean arterial pressure, intracranial pressure, CBF using laser Doppler flowmetry, and brain tissue NO concentrations using an NO electrode. In total, 41 rats were given either Epo (5000 U/kg) or saline s.

Comparison of tetrahydrobiopterin and L-arginine on cerebral blood flow after controlled cortical impact injury in rats.

The purpose of this study was to compare the effects of L-arginine and tetrahydrobiopterin administration on post-traumatic cerebral blood flow (CBF) and tissue levels of NO in injured brain tissue. Rats were anesthetized with isoflurane. Mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations were measured prior to, and for 2 h after a controlled cortical impact injury.

Laser Doppler flow and brain tissue PO2 after cortical impact injury complicated by secondary ischemia in rats treated with arginine.

Background: Traumatic brain injury (TBI) makes the brain susceptible to secondary insults such as ischemia. This study tested the hypothesis that L-arginine would increase regional CBF (rCBF) and brain tissue PO2 (PbtO2) at the injury site.

Methods: A secondary insult model was employed in rodents.

Oxidative DNA lesions in a rodent model of traumatic brain injury.

Background: Oxidative DNA lesions have not been well studied in traumatic brain injury (TBI).

Methods: TBI was induced with a controlled cortical impact injury in rats. Brain tissue was examined for 8-hydroxy-2'-deoxyguanosine (oh8dG) using mono-clonal antibodies at different time frames; 15 minutes (n = 4), 30 minutes (n = 7), 60 minutes (n = 6), and 240 minutes (n = 5).

Nitric oxide in traumatic brain injury.

Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours-days later.

The role of endothelial nitric oxide synthase in the cerebral hemodynamics after controlled cortical impact injury in mice.

Traumatic brain injury causes a reduction in cerebral blood flow, which may cause additional damage to the brain. The purpose of this study was to examine the role of nitric oxide produced by endothelial nitric oxide synthase (eNOS) in these vascular effects of trauma. To accomplish this, cerebral hemodynamics were monitored in mice deficient in eNOS and wild-type control mice that underwent lateral controlled cortical impact injury followed by administration of either L-arginine, 300 mg/kg, or saline at 5 min after the impact injury.

L-arginine and free radical scavengers increase cerebral blood flow and brain tissue nitric oxide concentrations after controlled cortical impact injury in rats.

To examine the mechanism of the increase in cerebral blood flow induced by L-arginine administration after traumatic brain injury, the cerebral hemodynamic effects of L-arginine, D-arginine, and the free radical scavengers superoxide dismutase (SOD) and catalase were compared in the controlled cortical impact injury model in rats. Animals were anesthetized with isoflurane. Measured parameters included mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations using an NO electrode.

Neuroprotective effects of L-arginine administration after cortical impact injury in rats: dose response and time window.

Administration of L-arginine has been shown to increase cerebral blood flow and reduce neurological damage after experimental traumatic brain injury. The purpose of this study was to examine the optimal dose and time window for these neuroprotective effects. In a dose response experiment, doses of L-arginine ranging from 37.