Departments of aNeurology and Developmental Medicine bNeuroscience, Kennedy Krieger Research Institute Departments of cNeurology dPediatrics eNeuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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.
[Show abstract][Hide abstract] ABSTRACT: A parallel constrained coding scheme is considered where p-blocks
of raw data are encoded simultaneously into q tracks such that the
contents of each track belong to a given constraint S. It is shown that
as q increases, there are parallel block-decodable encoders for S whose
coding ratio p/q converges to the capacity of S. Examples are provided
where parallel coding allows block-decodable encoders, while
conventional coding, at the same rate, does not. Parallel encoders are
then applied as building blocks in the construction of block-decodable
encoders for certain families of two-dimensional constraints
IEEE Transactions on Information Theory 06/2002; 48(5-48):1009 - 1020. DOI:10.1109/18.995538 · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recombinant human erythropoietin (rEpo) is neuroprotective in neonatal models of hypoxic-ischemic brain injury. However, the optimal rEpo dose, dosing interval, and number of doses for reducing brain injury are still undetermined. We compared the neuroprotective efficacy of several subcutaneous rEpo treatment regimens. Seven-day-old rats underwent unilateral carotid ligation plus 90 min 8% hypoxia. Treatment began immediately after injury. Treatment regimens examined included 1, 3, or 7 daily subcutaneous injections of either 0 (vehicle), 2,500, 5,000, or 30,000 U/kg rEpo. Gross brain injury, neuronal apoptosis (TUNEL), and gliosis (glial fibrillary acidic protein) were assessed at 48 h or 1 wk post injury. Immunoreactive cells and brain injury were quantified for statistical comparison to vehicle controls. rEpo treatment reduced brain injury, apoptosis, and gliosis, in a dose-dependent U-shaped manner at both 48 h and 1 wk. Neither one injection of 2,500, seven injections of 5,000, or three injections of 30,000 U/kg rEpo were protective. Three doses of 5,000 and one dose of 30,000 U/kg rEpo were most protective at both time intervals. rEpo provides dose-dependent neuroprotection. Of the regimens tested, three doses of 5,000 U/kg was optimal because it provided maximal benefit with limited total exposure.
Pediatric Research 05/2007; 61(4):451-5. DOI:10.1203/pdr.0b013e3180332cec · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enhanced glutamate release and inflammation play an important role in the pathogenesis of developmental brain injury. Although N-methyl-d-aspartate receptor (NMDAR) antagonists potently attenuate neonatal brain damage in several animal models, they can also impact trophic functions in the developing brain. As a consequence, high-affinity NMDAR antagonists have been shown to trigger widespread apoptotic neurodegeneration in the newborn brain. Dextromethorphan (DM), a low-affinity NMDAR antagonist with anti-inflammatory properties, may be neuroprotective against excitotoxic and inflammation-enhanced excitotoxic brain injury, without the associated stimulation of apoptotic degeneration. Using an established newborn mouse model of excitotoxic brain damage, we determined whether systemic injection of DM significantly attenuates excitotoxic lesion size. We investigated several doses and time regimens; a dose of 5 microg/g DM given in a combination of both pre-injury and repetitive post-injury treatment proved most effective. DM treatment significantly reduced lesion size in gray and white matter by reducing cell death as shown by a decreased Fluoro-Jade B staining and caspase-3 activation. Pre-treatment with interleukin-1beta and lipopolysaccharide enhanced NMDAR-mediated excitotoxic brain injury and microglial cell activation. This sensitizing effect was abolished by DM treatment, as the effectiveness of DM in reducing lesion size and microglial cell activation was similar to phosphate-buffered saline-pre-treated controls. In all cases, no gender-specific differences were detected. DM treatment did not trigger any apoptotic neurodegeneration (caspase-3 cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, Fluoro-Jade B staining). Although functional parameters were not measured, our data corroborate reports that DM is neuroprotective and that it may therefore improve functional outcome following perinatal brain injury.
European Journal of Neuroscience 03/2008; 27(4):874-83. DOI:10.1111/j.1460-9568.2008.06062.x · 3.18 Impact Factor
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