The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform

Edward D. Hall - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of lipid peroxidation in central Nervous System Trauma and ischemia.
    Journal of the neurological sciences, 1995
    Co-Authors: Edward D. Hall
    Abstract:

    A novel group of compounds, the 21-aminosteroids ("lazaroids"), have been designed that are potent inhibitors of oxygen free radical-induced, iron-catalyzed lipid peroxidation (LP) in microvascular and Nervous tissue. One of these, tirilazad mesylate (U-74006F), has been selected for clinical evaluation as a cerebroprotective agent. In vitro studies suggest that tirilazad exerts its antioxidant activity by multiple mechanisms including: increasing membrane stability, scavenging of lipid peroxyl radicals, reducing LP-induced arachidonic acid release, decreased formation or scavenging of hydroxyl radicals, and maintenance of the levels of endogenous vitamin E. The major site of action appears to be the blood-brain barrier based upon its known localization in cerebrovascular endothelium and numerous studies showing an attenuation of subarachnoid hemorrhage (SAH), injury, and ischemia-induced blood-brain barrier permeability. Tirilazad has demonstrated neuroprotective efficacy in multiple preclinical models of spinal cord and head injury, SAH, and focal cerebral ischemia, as measured by a decrease in cerebral vasospasm, blood-brain barrier compromise, post-Traumatic ischemia, edema, ischemic neuronal necrosis and infarction, and improved neurological recovery. This efficacy is correlated with a reduction in markers of oxygen radical-induced LP. Phase III clinical trials are currently ongoing in spinal cord and head injury, SAH, and ischemic stroke. Initial results from a European/Australian/New Zealand trial in SAH have shown a significant decrease in mortality and an increase in the incidence of good recovery.

  • Role of Oxygen Radicals in Central Nervous System Trauma
    Oxygen Free Radicals in Tissue Damage, 1993
    Co-Authors: Edward D. Hall
    Abstract:

    There is now extensive experimental support for the early occurrence and pathophysiological importance of oxygen radical formation and cell membrane lipid peroxidation in the injured Nervous System (Braughler and Hall, 1989; Demopoulos et al., 1980; Hall and Braughler, 1986; Kontos and Povlishock, 1986). The radical-initiated peroxidation of neuronal, glial, and vascular cell membranes and myelin is catalyzed by free iron released from hemoglobin, transferrin, and ferritin by either lowered tissue pH or oxygen radicals. If unchecked, lipid peroxidation is a geometrically progressing process that will spread over the surface of the cell membrane causing impairment to phospholipid-dependent enzymes, disruption of ionic gradients and, if severe enough, membrane lysis.

  • 2-(Aminomethyl)chromans that inhibit iron-dependent lipid peroxidation and protect against central Nervous System Trauma and ischemia.
    Journal of medicinal chemistry, 1992
    Co-Authors: Eric Jon Jacobsen, Edward D. Hall, Donald E. Ayer, K. L. Belonga, David J. Houser
    Abstract:

    A series of 2-(aminomethyl)chromans was developed as potent inhibitors of iron-dependent lipid peroxidation. Compounds within this class are extremely effective at inhibiting lipid peroxidation with IC50's as low as 0.2 microM. Selected members were found to enhance early neurological recovery and survival in a mouse head injury model. In this assay, improvement in the 1-h post-head-injury neurological status (grip test score) by as much as 230% of control was observed. One of the most efficacious compounds (35) was evaluated in two models of cerebral ischemia where significant neuroprotection was observed. These results provide further support for the importance of cerebroprotective antioxidants for the treatment of Traumatic and ischemic injury as well as additional evidence for the role of oxygen radicals in postischemic brain damage.

Arthur M. Lam - One of the best experts on this subject based on the ideXlab platform.

  • Management of central Nervous System Trauma
    Current Opinion in Anaesthesiology, 1993
    Co-Authors: T. S. Mayberg, Arthur M. Lam
    Abstract:

    Head Trauma continues to be an epidemic affecting young people, primarily as a result of motor vehicle accidents. Recent advances center on the identification of ischemia as an important contributing factor to secondary injury. Use of transcranial Doppler and continuous jugular venous oximetry are reviewed. New modalities of treatment are also discussed.

T. S. Mayberg - One of the best experts on this subject based on the ideXlab platform.

  • Management of central Nervous System Trauma
    Current Opinion in Anaesthesiology, 1993
    Co-Authors: T. S. Mayberg, Arthur M. Lam
    Abstract:

    Head Trauma continues to be an epidemic affecting young people, primarily as a result of motor vehicle accidents. Recent advances center on the identification of ischemia as an important contributing factor to secondary injury. Use of transcranial Doppler and continuous jugular venous oximetry are reviewed. New modalities of treatment are also discussed.

Jeffrey R. Kirsch - One of the best experts on this subject based on the ideXlab platform.

  • Clinical Anesthesia in Neurosurgery
    Anesthesiology, 1991
    Co-Authors: Elizabeth A. M. Frost, Jeffrey R. Kirsch
    Abstract:

    Cerebral physiology and evaluation cerebral hemodynamics and metabolism physiology of intracranial pressure electrophysiologic monitoring effects of anesthetic agents on intracranial dynamics anesthetic management for neuroradiologic diagnostic procedures fluid and electrolyte balance in neurosurgical patients neurosurgical and related procedures the management of cerebrovascular disease posterior cranial fossa surgery brain tumours surgery of the spine peripheral nerve surgery pediatric neurologic surgery surgery for seizures pain therapy stereotactic surgery central Nervous System Trauma the management of head injury cardiovascular effects of severe head injury management of spinal cord Trauma anesthetic management of patients with neurologic disease for non-neurosurgical procedures post-operative and intensive care post-anesthetic care neurosurgical intensive care hyperalimentation therapy following major brain insult cerebral death brain death.

Riyi Shi - One of the best experts on this subject based on the ideXlab platform.

  • Acrolein-mediated injury in Nervous System Trauma and diseases.
    Molecular nutrition & food research, 2011
    Co-Authors: Riyi Shi, Todd Rickett, Wenjing Sun
    Abstract:

    Acrolein, an α,β-unsaturated aldehyde, is a ubiquitous pollutant that is also produced endogenously through lipid peroxidation. This compound is hundreds of times more reactive than other aldehydes such as 4-hydroxynonenal, is produced at much higher concentrations, and persists in solution for much longer than better known free radicals. It has been implicated in disease states known to involve chronic oxidative stress, particularly spinal cord injury and multiple sclerosis. Acrolein may overwhelm the anti-oxidative Systems of any cell by depleting glutathione reserves, preventing glutathione regeneration, and inactivating protective enzymes. On the cellular level, acrolein exposure can cause membrane damage, mitochondrial dysfunction, and myelin disruption. Such pathologies can be exacerbated by increased concentrations or duration of exposure, and can occur in normal tissue incubated with injured spinal cord, showing that acrolein can act as a diffusive agent, spreading secondary injury. Several chemical species are capable of binding and inactivating acrolein. Hydralazine in particular can reduce acrolein concentrations and inhibit acrolein-mediated pathologies in vivo. Acrolein scavenging appears to be a novel effective treatment, which is primed for rapid translation to the clinic.

  • Accumulation of Acrolein–Protein Adducts after Traumatic Spinal Cord Injury
    Neurochemical Research, 2005
    Co-Authors: Jian Luo, Koji Uchida, Riyi Shi
    Abstract:

    Reactive oxygen species and resultant lipid peroxidation (LPO) have been associated with central Nervous System Trauma. Acrolein (2-propenal) and 4-hydroxynonenal (HNE) are the most toxic byproducts of LPO, with detrimental effects in various types of cells. In this study, we used immunoblotting techniques to detect the accumulation of protein-bound acrolein and HNE. We report that protein-bound acrolein and HNE were significantly increased in guinea pig spinal cord following a controlled compression injury. The acrolein and HNE protein-adducts increased in the damaged spinal cord as early as 4 h after injury, reached a peak at 24 h after injury, and remained at a significantly high level up to 7 days after injury. Such increase of protein adducts was also observed in the adjacent segments of the injury site beginning at 24 h post injury. These results suggest that products of lipid peroxidation, especially acrolein, may play a critical role in the secondary neuronal degeneration, which follows mechanical insults.