Central nervous system trauma and strokeII. Physiological and pharmacological evidence for involvement of oxygen radicals and lipid peroxidation

Hall, Edward D.; Braughler, J M

doi:10.1016/0891-5849(89)90057-9

Cited by 551 publications

(187 citation statements)

References 80 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…There is evidence for the importance of oxygen radical formation and cellmembrane lipid peroxidation in the injured nervous system. 9,10,30,31 Lipid peroxidation is a progressing process that spreads over the surface of the cell membrane, inhibiting lipid dependent enzymes, disrupting ionic gradients, and, if severe enough, lysing membranes. 32 Many researchers have shown that agents inhibiting lipid peroxidation enhance functional recovery in experimental CNS injuries.…”

Section: Discussionmentioning

confidence: 99%

The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury

et al. 1998

View full text Add to dashboard Cite

Study Design: The e ect of epidural space perfusion with chilled saline solution (% 0.9 NaCl) on lipid peroxidation after experimental spinal cord injury in rats was evaluated. Objectives: The extent of lipid peroxidation is a useful parameter for evaluating the cellular disturbance caused by spinal cord trauma in experimental conditions. The protective e ects of hypothermia against neurological injury resulting from trauma or ischemia both in experimental and clinical situations have been demonstrated. Setting: Departments of Neurosurgery and Biochemistry, Cerrahpasa Medical School, Istanbul, Turkey. Methods: Twenty-®ve female Wistar Albino rats were used. There were ®ve rats in group I (sham-operated), seven rats in group II (trauma), and eight rats in group III (epidural cooling). The remaining ®ve rats were used for the pilot study to determine the spinal cord and body temperature. A clip compression method was used to produce acute spinal cord injury. In group III, 30 min after the trauma the injured spinal cord was cooled by perfusion of the epidural space with chilled saline solution (% 0.9 NaCl) with a¯ow rate of 5 ml/min for 30 min. At 2 h after trauma, all rats other than the ones used in the pilot study, were sacri®ced and the spinal cords were excised. The extent of lipid peroxidation in the spinal cord was assessed by measuring the tissue content of malonil dialdehyde (MDA). Results: The tissue MDA contents were 1.58 micromol MDA/gram wet weight (gww) in group 1 (sham-operated), 2.58 micromol MDA/gww in group 2 (trauma), and 1.77 micromol/ gww in group 3 (epidural cooling), the di erences being statistically signi®cant. Conclusion:The results indicated that epidural cooling of traumatized spinal cord is e ective in preventing secondary damage due to the peroxidation of lipid membranes.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Tamoxifen, or its immediate metabolite 4-hydroxytamoxifen, are effective antioxidants (Dubey et al, 1999;Wiseman et al, 1994), and antioxidants have been clearly shown to be protective in brain trauma and stroke (Hall et al, 1989;Chan, 1999). The major tamoxifen metabolite, 4-OH tamoxifen was shown to markedly reduce induced lipid peroxidation in brain mitochondria in vitro (Moreira et al, 2004), but the antioxidative effects of tamoxifen have never been directly tested in stroke models.…”

Section: Antioxidant Activity and Tamoxifen-induced Neuroprotectionmentioning

confidence: 99%

“…Since all these effects are included within our current knowledge of the damaging processes set in motion by cerebral ischemia (Chan, 1999;Dirnagl et al, 1999;Ginsberg, 2003;Hall and Braughler, 1989;Stroke therapy academic industry round table, 1999), we are tempted to ascribe a causal relation between these demonstrated effects of tamoxifen and its neuroprotection. Further studies on tamoxifen pharmacokinetics in order to relate dosing to blood and CNS levels and the concentrations and times at which different processes can be inhibited can be used to further support these associations and allow more rational design of any proposed clinical trials.…”

Section: Antioxidant Activity and Tamoxifen-induced Neuroprotectionmentioning

confidence: 99%

Neuroprotection by tamoxifen in focal cerebral ischemia is not mediated by an agonist action at estrogen receptors but is associated with antioxidant activity

Zhang

Milatović²,

Aschner³

et al. 2007

Experimental Neurology

View full text Add to dashboard Cite

We have previously shown that tamoxifen can induce marked neuroprotection after middle cerebral artery occlusion (MCAo) in rats and have described two possible mechanisms of action: namely inhibition of EAA release and inhibition of nNOS activity. In this study we tested other potential mechanisms. Namely, agonist action at estrogen receptors and an antioxidative action. Tamoxifentreated rats had significantly improved neurobehavioral deficit scores after 24 hours and showed ∼75% reduced infarct volumes. These were unaffected by ICI 182,780 (a high affinity and pure receptor antagonist) administered intravenously, or intracisternally to avoid possible lack of brain penetration, 15 minutes before intravenous administration of tamoxifen. In rats subjected to 2 hours MCAo followed by 22 hours reperfusion, a 1.8-fold and 2.9-fold increase of F 2 -IsoPs and F 4 neuroprostanes, respectively, as relatively stable markers of oxidative damage, were measured in the ischemic hemisphere compared with the corresponding contralateral hemisphere or sham controls. Tamoxifen given at 3 hours after the start of ischemia reduced the IsoPs and NeuroPs to sham control levels, and also inhibited their production by chemically induced lipid peroxidation in brain homogenates. These data are consistent with at least part of tamoxifen's marked neuroprotection in focal cerebral ischemic injury being due to its antioxidant activity but not by an acute action on estrogen receptors (212 words).

show abstract

“…Despite the absence of a clear understanding of their significance in tissue trauma or injury, observations in neuroscience and pharmacologically based literature strongly implicate an important function for oxygen radicals in trauma and stroke (1,2). Accordingly, pharmacological approaches to protecting and/or treating CNS tissue injury due to trauma or stroke includes effective antioxidants (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…Brain microvessel endothelial cells (BMECs) were labeled with well-known fluorophores, 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethyammoniumphenyl)-6-diphenyl-1,3,5-hexatriene, ptoluenesulfonate (TMA-DPH), and fluorescence anisotropy and lifetime measures of these probes used to examine the interactions of 21-aminosteroids with cellular lipid domains (7)(8)(9)(10)(11). BMECs represented an appropriate experimental system since the microvasculature of the central nervous system has been suggested as a major target for oxygen radicals in trauma and stroke (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

21-aminosteroid and 2-(aminomethyl)chromans inhibition of arachidonic acid-induced lipid peroxidation and permeability enhancement in bovine brain microvessel endothelial cell monolayers

Shi

Cavitt

Audus

1995

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Abstract:Studies were conducted to demonstrate 21-aminosteroid distribution into the hydrophobic or lipid domains of biological membranes, a presumed site at which these compounds inhibit lipid peroxidation. Bovine brain microvessel endothelial cells (BMECs) were labeled with diphenylhexatriene fluorophores and interactions with cell membranes characterized with fluorescence anisotropy and lifetimes. Two 21-aminosteroids (U-74500A and U74006F) were shown to preferentially alter the fluorescence anisotropy and lifetime parameters of the diphenylhexatriene probe distributing into membranes throughout the BMECs. Little or no effect of the compounds on the fluorescence parameters of the diphenylhexatriene probe the localized on the surface of BMEC plasma membranes. By contrast, cholesterol used as a positive control altered substantially the fluorescence parameters of BMECs labeled with either diphenylhexatriene probe. Results suggest 21-aminosteroid-induced changes in the molecular packing order and drug:fluorescent probe interactions in membrane hydrophobic (or lipid) domains throughout the BMEC. Concentrations of 21-aminosteroids altering the fluorescence parameters of diphenylhexatriene labeled BMECs correspond to those concentrations of 21-aminosteroids effective in vitro in inhibition lipid peroxidation. Evidence for 21-aminosteroid association with the hydrophobic domains in brain microvessel endothelial cells. Free Rad. Biol. Med. 11, 361-371. PMID: 1797623. Publisher's official version: http://dx

show abstract

Central nervous system trauma and strokeII. Physiological and pharmacological evidence for involvement of oxygen radicals and lipid peroxidation

Cited by 551 publications

References 80 publications

The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury

The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury

Neuroprotection by tamoxifen in focal cerebral ischemia is not mediated by an agonist action at estrogen receptors but is associated with antioxidant activity

21-aminosteroid and 2-(aminomethyl)chromans inhibition of arachidonic acid-induced lipid peroxidation and permeability enhancement in bovine brain microvessel endothelial cell monolayers

Contact Info

Product

Resources

About