Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage

Germanò, Antonino; Imperatore, C.; D’Avella, Domenico; Costa, Giovanni; Tomasello, Francesco

doi:10.3171/jns.1998.88.6.1075

Cited by 39 publications

(28 citation statements)

References 37 publications

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“…The importance of antioxidant treatment in preventing neuronal damage has recently been emphasized (23,(59)(60)(61). Vitamin E (62) and a novel free radical scavenger (59) protect against changes in membrane permeability caused by peroxidation and attenuate ischemic and postischemic brain swelling.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats.

et al. 2000

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Both chronic hyperglycemia and ischemia/reperfusion (IR) cause an imbalance in the oxidative state of tissues. Normoglycemic and streptozotocin (STZ)-diabetic rats were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 60 min. Rats had either been treated with dehydroepiandrosterone (DHEA) for 7, 14, or 21 days (2 or 4 mg/day per rat) or left untreated. Oxidative state, antioxidant balance, and membrane integrity were evaluated in isolated synaptosomes. IR increased the levels of reactive species and worsened the synaptic function, affecting membrane Na/K-ATPase activity and lactate dehydrogenase release in all rats. The oxidative imbalance was much severer when transient IR was induced in STZ-diabetic rats. DHEA treatment restored H 2 O 2 , hydroxyl radical, and reactive oxygen species to close to control levels in normoglycemic rats and significantly reduced the level of all reactive species in STZ-diabetic rats. Moreover, DHEA treatment counteracted the detrimental effect of IR on membrane integrity and function: the increase of lactate dehydrogenase release and the drop in Na/K-ATPase activity were significantly prevented in both normoglycemic and STZ-diabetic rats. The results confirm that DHEA, an adrenal steroid that is synthesized de novo by brain neurons and astrocytes, possesses a multitargeted antioxidant effect. They also show that DHEA treatment is effective in preventing both derangement of the oxidative state and neuronal damage induced by IR in experimental diabetes. Diabetes

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Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats.

et al. 2000

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“…Bilirubin oxidation products (BOXes) may have a similar time course to onset of vasospasm, and they are vasoactive both in vivo and in vitro (Clark et al, 2002). Evidence that oxidative stress may contribute to vasospasm (cerebral and coronary) has been published (Gaetani et al, 1998;Kahler et al, 2001;Matz et al, 1996;Polidori et al, 1997;Reeder et al, 2002); however, antioxidant therapy alone has not proven clinically effective, and is not standard of care (Asano et al, 1984;Asano et al, 1996;Germano et al, 1998;Luo et al, 1995). Thus, oxidative stress alone may not be the sole cause of vasospasm.…”

Section: Introductionmentioning

confidence: 99%

Bilirubin Production and Oxidation in CSF of Patients with Cerebral Vasospasm after Subarachnoid Hemorrhage

Pyne‐Geithman

Morgan

Wagner

et al. 2005

J Cereb Blood Flow Metab

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Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) remains a significant cause of mortality and morbidity; however, the etiology is, as yet, unknown, despite intensive research efforts. Research in this laboratory indicates that bilirubin and oxidative stress may be responsible by leading to formation of bilirubin oxidation products (BOXes), so we investigated changes in bilirubin concentration and oxidative stress in vitro, and in cerebral spinal fluid (CSF) from SAH patients. Non-SAH CSF, a source of heme oxygenase I (HO-1), and blood were incubated, and in vitro bilirubin production measured. Cerebrospinal fluid from SAH patients was collected, categorized using stimulation of vascular smooth muscle metabolism in vitro, and information obtained regarding occurrence of vasospasm in the patients. Cerebral spinal fluid was analyzed for hemoglobin, total protein and bilirubin, BOXes, malonyldialdehyde and peroxidized lipids (indicators of an oxidizing environment), and HO-1 concentration. The formation of bilirubin in vitro requires that CSF is present, as well as whole, non-anti-coagulated blood. Bilirubin, BOXes, HO-1, and peroxidized lipid content were significantly higher in CSF from SAH patients with vasospasm, compared with nonvasospasm SAH CSF, and correlated with occurrence of vasospasm. We conclude that vasospasm may be more likely in patients with elevated BOXes. The conditions necessary for the formation of BOXes are indeed present in CSF from SAH patients with vasospasm, but not CSF from SAH patients without vasospasm.

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“…Thus, on the basis of the aforementioned ROS cascadepromoting reactions, a variety of antioxidants such as SOD, 9 the ⅐OH scavenger AVS [(ϩ/Ϫ)-N, NЈ-propylenedinicotinamide], 11,13 ebselen (an agent exhibiting glutathione peroxidase-like activity), 12,14 the antioxidant aminosteroid, 7,8 the singlet oxygen scavenger histidine, 10 and iron chelators [15][16][17] have been shown to be prophylactic against cerebral vasospasm in animal models as well as in SAH patients. Of particular interest is the Fe 2ϩ chelator 2,2Ј-dipyridyl, which has been shown to completely prevent delayed vasospasm in a primate model of SAH, 17 pointing to an important role of the Fe 2ϩ iron ion in the pathogenesis of cerebral vasospasm, as ROS formation requires the ferrous moiety and Fe 2ϩ is a potent trapping agent for NO.…”

Section: Possible Origin Of ⅐Omentioning

confidence: 99%

“…5,6 In support of the theory that ROS are primary pathogens for SAH, a variety of antioxidants have been shown to attenuate cerebral vasospasm in animals and humans. [7][8][9][10][11][12][13][14] We have shown that intracisternal overproduction of ⅐O 2 Ϫ may initiate and/or mediate cerebral arterial vasoconstriction and subsequent structural damage. 3 Moreover, administration of ferrous (Fe 2ϩ ) or ferric (Fe 3ϩ ) iron chelators was shown to mitigate against cerebral vasospasm, providing evidence that the iron-catalyzed Haber-Weiss and Fenton reactions are involved in the mechanism of ROS generation leading to the occurrence of cerebral vasospasm.…”

mentioning

confidence: 99%

Intracisternal Increase of Superoxide Anion Production in a Canine Subarachnoid Hemorrhage Model

Mori

Nagata

Town

et al. 2001

Stroke

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Background and Purpose-Reactive oxygen species (ROS) are thought to be primary in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, as direct evidence of ROS has not yet been demonstrated in cerebral vasospasm, we sought to substantiate superoxide anion (⅐O 2 Ϫ ) generation in the subarachnoid space after SAH using a modification of Karnovsky's manganese/diaminobenzidine (Mn 2ϩ /DAB) technique. Methods-SAH or sham operation was induced according to a 2-hemorrhage model in a total of 24 beagle dogs. On day 2 or 7 after SAH or sham operation, dogs were intrathecally infused with buffer containing Mn 2ϩ and DAB, and the brain stem was prepared for light and electron microscopy. Possible colocalization of ferrous (Fe 2ϩ ) or ferric (Fe 3ϩ ) iron ions with ⅐O 2 Ϫ was also examined with the use of Turnbull blue or Berlin blue staining, respectively. Results-Light microscopy revealed amorphous, amber deposits within the subarachnoid hematoma, the periarterial space, and the tunica adventitia of the basilar artery on days 2 and 7 after SAH. ⅐O 2 Ϫ deposits were eliminated by addition of superoxide dismutase or exclusion of either Mn 2ϩ or DAB from the perfusate, confirming the specificity of the reaction. These deposits were colocalized with blue reaction deposits indicating

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Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage

Abstract: These results demonstrate useful antivasospastic and brain-protective actions of AVS after induction of experimental SAH and provide support for observations of beneficial effects of AVS made in the clinical setting.

Cited by 39 publications

References 37 publications

Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats.

Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats.

Bilirubin Production and Oxidation in CSF of Patients with Cerebral Vasospasm after Subarachnoid Hemorrhage

Intracisternal Increase of Superoxide Anion Production in a Canine Subarachnoid Hemorrhage Model

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