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ABSTRACT: The non-competitive N-methyl-D-aspartate receptor antagonist dextromethorphan is protective against some types of brain injury. Unilateral carotid ligation in postnatal day 12 CD1 mice produces ischemic brain injury. To evaluate the neuroprotective potential of dextromethorphan against ischemic injury in the immature brain, seven litters of postnatal day 12 CD1 mice received either dextromethorphan or vehicle after a unilateral carotid ligation. Only the male pups were protected, and brain injury was unchanged in the female pups treated with dextromethorphan. These results suggest that dextromethorphan neuroprotection against ischemic injury in the immature brain is sex-dependent.
Neuroreport 09/2006; 17(12):1319-22. · 1.66 Impact Factor
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ABSTRACT: Sturge-Weber syndrome presents with vascular malformations of the brain, skin, and eye. Fibronectin has potent effects on angiogenesis, vessel remodeling, and vessel innervation density. To determine fibronectin expression in the blood vessels of Sturge-Weber syndrome brain and skin tissue and to quantify the density and circumference of Sturge-Weber syndrome blood vessels by type compared with controls, we performed in situ hybridization for fibronectin messenger ribonucleic acid (RNA) expression on six Sturge-Weber syndrome cortical brain samples, six epilepsy brain samples, skin from two port-wine stain skin lesions, and two normal skin samples from two subjects with Sturge-Weber syndrome. Fibronectin messenger RNA was expressed in blood vessels and endothelial cells in the parenchyma of both Sturge-Weber syndrome and control brain tissues and in skin samples. Fibronectin expression was significantly reduced by 23% in the Sturge-Weber syndrome meningeal vessels compared with the epilepsy controls (P < .01). Fibronectin expression was significantly increased by 19% in the Sturge-Weber syndrome parenchymal vessels compared with the epilepsy controls (P < .05). No difference was found in the expression of fibronectin in port-wine stain skin blood vessels. The density of leptomeningeal blood vessels in the Sturge-Weber syndrome brain tissue samples was 45% greater than in the epilepsy samples (P < .05). Blood vessel circumference was significantly decreased in the Sturge-Weber syndrome meningeal vessels compared with the controls (27%; P < .05). When blood vessels from different brain regions were compared, fibronectin expression was decreased in Sturge-Weber syndrome meningeal vessels and was increased in the parenchymal vessels. Altered blood vessel fibronectin expression in Sturge-Weber syndrome could contribute to abnormal vascular structure and function in this disorder.
Journal of Child Neurology 08/2005; 20(7):572-7. · 1.75 Impact Factor
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ABSTRACT: Ischemic brain injury from stroke is an important cause of disability in infants and children, but current experimental models for the disorder are complex. These preparations require occlusion of small intracerebral vessels or common carotid artery ligation combined with exposure to reduced levels of oxygen. Unilateral carotid artery ligation alone was sufficient to cause brain injury in more than 70% of 12-day-old CD1 mice. Using a blinded behavioral rating scale of seizure activity in mice, a direct, highly significant correlation between the severity of seizures over the 4-hour period after ligation and the severity of histologic brain injury 7 days later (Spearman's rho = 0.835, P < 0.001) was documented. This study presents the first model of stroke in immature mice produced by unilateral carotid artery ligation alone, and the first to demonstrate a clear correlation between acute ischemia-induced seizures and brain injury. This new model should be useful for examining the pathogenesis of stroke in the immature brain and the potential contribution of seizures to final outcome.
Pediatric Neurology 10/2004; 31(4):254-7. · 1.52 Impact Factor
