The Experts below are selected from a list of 24 Experts worldwide ranked by ideXlab platform
Earl F. Ellis - One of the best experts on this subject based on the ideXlab platform.
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Stretch-induced injury of cultured neuronal, glial, and endothelial cells. Effect of polyethylene glycol-conjugated superoxide dismutase
Stroke, 1996Co-Authors: Jerry S. Mckinney, Karen A. Willoughby, Shi Liang, Earl F. EllisAbstract:Background and Purpose There is abundant evidence that after in vivo traumatic brain injury, oxygen radicals contribute to changes in cerebrovascular structure and function; however, the cellular source of these oxygen radicals is not clear. The purpose of these experiments was to use a newly developed in vitro tissue culture model to elucidate the effect of strain, or stretch, on neuronal, glial, and endothelial cells and to determine the effect of the free radical scavenger polyethylene glycol–conjugated superoxide dismutase (PEG-SOD; Pegorgotein, Dismutec) on the response of each cell type to trauma. Methods Rat brain astrocytes, neuronal plus glial cells, and aortic endothelial cells were grown in cell culture wells with 2-mm-thick silastic membrane bottoms. A controllable, 50-millisecond pressure pulse was used to transiently deform the silastic membrane and thus stretch the cells. Injury was assessed by quantifying the number of cells that took up the normally cell-impermeable dye propidium iodide. ...
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The effect of postinjury administration of polyethylene glycol-conjugated superoxide dismutase (Pegorgotein, Dismutec) or lidocaine on behavioral function following fluid-percussion brain injury in rats.
Journal of neurotrauma, 1996Co-Authors: Robert J. Hamm, Meredith D. Temple, Brian R. Pike, Earl F. EllisAbstract:ABSTRACT Previous studies in our laboratory have shown that polyethylene glycol-conjugated Superoxide dismutase (PEG-SOD) or lidocaine treatment before experimental fluid-percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to determine if posttreatment with PEG-SOD or lidocaine is also associated with changes in the trauma-induced suppression of motor and cognitive function that occurs following traumatic brain injury (TBI). Twenty-four hours after surgical preparation, rats were randomly assigned to a saline or drug posttreatment group, PEG-SOD (Pegorgotein, Dismutec®, 10,000 IU/kg) or lidocaine (2 mg/kg), which was injected iv 30 min after moderate injury. PEG-SOD completely prevented beam walk latency deficits on days 1–5 postinjury while lidocaine similarly prevented beam walk deficits on days 2 through 5 postinjury. Both drugs produced a statistically insignificant trend for a decrease in beam balanc...
Aaron M. Cook - One of the best experts on this subject based on the ideXlab platform.
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A Review of Neuroprotection Pharmacology and Therapies in Patients with Acute Traumatic Brain Injury
CNS Drugs, 2012Co-Authors: Kevin W. Mcconeghy, Jimmi Hatton, Lindsey Hughes, Aaron M. CookAbstract:Traumatic brain injury (TBI) affects 1.6 million Americans annually. The injury severity impacts the overall outcome and likelihood for survival. Current treatment of acute TBI includes surgical intervention and supportive care therapies. Treatment of elevated intracranial pressure and optimizing cerebral perfusion are cornerstones of current therapy. These approaches do not directly address the secondary neurological sequelae that lead to continued brain injury after TBI. Depending on injury severity, a complex cascade of processes are activated and generate continued endogenous changes affecting cellular systems and overall outcome from the initial insult to the brain. Homeostatic cellular processes governing calcium influx, mitochondrial function, membrane stability, redox balance, blood flow and cytoskeletal structure often become dysfunctional after TBI. Interruption of this cascade has been the target of numerous pharmacotherapeutic agents investigated over the last two decades. Many agents such as selfotel, Pegorgotein (PEG-SOD), magnesium, deltibant and dexanabinol were ineffective in clinical trials. While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending. Consequently, no neuroprotective treatment options currently exist that improve neurological outcome after TBI. Investigations to date have extended understanding of the injury mechanisms and sites for intervention. Examination of novel strategies addressing both pathological and pharmacological factors affecting outcome, employing novel trial design methods and utilizing biomarkers validated to be reflective of the prognosis for TBI will facilitate progress in overcoming the obstacles identified from previous clinical trials.
J. Paul Muizelaar - One of the best experts on this subject based on the ideXlab platform.
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Clinical Trials with Dismutec™ (Pegorgotein; Polyethylene Glycol-Conjugated Superoxide Dismutase; PEG-SOD) in the Treatment of Severe Closed Head Injury
Advances in experimental medicine and biology, 1994Co-Authors: J. Paul MuizelaarAbstract:Although the suspicion for a role of oxygen radicals in disease and degeneration was raised a long time ago, the first publications relating free radicals with traumatic brain injury appeared only in 1981.1,2 Since then, however, a rapid development has taken place, culminating in a phase II human trial with a superoxide scavenger started in 19893 and several phase III clinical trials taking place at present. The initial laboratory experiments were concentrated on elucidating mechanisms for vascular damage after head injury. First, it was shown that in the early minutes after experimental fluid percussion injury in the cat, prostaglandin concentration in the brain increases, secondary to activation of the arachidonic acid pathway; this pathway leads to superoxide anion formation through the enzyme PGH synthase.1 Pretreatment with radical scavengers or with indomethacin, which inhibits cyclo-oxygenase and thus deprives the prostaglandin hydroperoxidase of substrate, protects the endothelium of the cerebral microcirculation from the effects of experimental brain injury.2 Subsequently, it was shown that immediately after the impact there is an increase in phospholipase C activity, which can release arachidonic acid in tissue, leading to oxygen radical formation.4 Further work showed that the radicals are produced not only in cerebral blood vessel walls but also in leukocytes and macrophages that accumulate in the brain between 3 and 24 hours after experimental injury.5 With the method used to identify the site of generation of the superoxide anion,6 only the vessel walls could be implicated in this process, but this is possibly because of insufficient penetration of the reagents into brain tissue.
Giovanni Rosa - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological perioperative brain neuroprotection: a qualitative review of randomized clinical trials
British Journal of Anaesthesia, 2013Co-Authors: Federico Bilotta, Adrian W. Gelb, Elisabetta Stazi, Luca Titi, F. P. Paoloni, Giovanni RosaAbstract:Summary Perioperative cerebral damage may be associated with surgery and anaesthesia. Pharmacological perioperative neuroprotection is associated with conflicting results. In this qualitative review of randomized controlled clinical trials on perioperative pharmacological brain neuroprotection, we report the effects of tested therapies on new postoperative neurological deficit, postoperative cognitive decline (POCD), and mortality rate. Studies were identified from Cochrane Central Register and MEDLINE and by hand-searching. Of 5904 retrieved studies, 25 randomized trials met our inclusion criteria. Tested therapies were: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate and xenon remacemide, atorvastatin, magnesium sulphate, erythropoietin, piracetam, rivastigmine, Pegorgotein, and 17β-estradiol. The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit. The use of lidocaine, ketamine, and magnesium sulphate was associated with controversial results on POCD. The POCD did not differ between treated patients and control group for other tested drugs (thiopental, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate, xenon, erythropoietin, remacemide, piracetam, rivastigmine, Pegorgotein, and 17β-estradiol). None of the tested drugs was associated with a reduction in mortality rate. Drugs with various mechanisms of action have been tested over time; current evidence suggests that pharmacological brain neuroprotection might reduce the incidence of new postoperative neurological deficits and POCD, while no benefits on perioperative mortality are described. Of importance from this review is the need for shared methodological approach when clinical studies on pharmacological neuroprotection are designed.
Kevin W. Mcconeghy - One of the best experts on this subject based on the ideXlab platform.
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A Review of Neuroprotection Pharmacology and Therapies in Patients with Acute Traumatic Brain Injury
CNS Drugs, 2012Co-Authors: Kevin W. Mcconeghy, Jimmi Hatton, Lindsey Hughes, Aaron M. CookAbstract:Traumatic brain injury (TBI) affects 1.6 million Americans annually. The injury severity impacts the overall outcome and likelihood for survival. Current treatment of acute TBI includes surgical intervention and supportive care therapies. Treatment of elevated intracranial pressure and optimizing cerebral perfusion are cornerstones of current therapy. These approaches do not directly address the secondary neurological sequelae that lead to continued brain injury after TBI. Depending on injury severity, a complex cascade of processes are activated and generate continued endogenous changes affecting cellular systems and overall outcome from the initial insult to the brain. Homeostatic cellular processes governing calcium influx, mitochondrial function, membrane stability, redox balance, blood flow and cytoskeletal structure often become dysfunctional after TBI. Interruption of this cascade has been the target of numerous pharmacotherapeutic agents investigated over the last two decades. Many agents such as selfotel, Pegorgotein (PEG-SOD), magnesium, deltibant and dexanabinol were ineffective in clinical trials. While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending. Consequently, no neuroprotective treatment options currently exist that improve neurological outcome after TBI. Investigations to date have extended understanding of the injury mechanisms and sites for intervention. Examination of novel strategies addressing both pathological and pharmacological factors affecting outcome, employing novel trial design methods and utilizing biomarkers validated to be reflective of the prognosis for TBI will facilitate progress in overcoming the obstacles identified from previous clinical trials.