Eain M. Cornford

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The blood-brain barrier permeability to certain 14-C-labelled purine and pyrimidine compounds was studied by simultaneous injection in conjunction with two reference isotopes into the rat common carotid artery and decapitation 15s later. The amount of 14-C-labelled base or nucleoside remaining in brain was expressed in relation to 3-H2O (a highly diffusible(More)
Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause Lafora disease (LD), a progressive and invariably fatal epilepsy with periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions (Lafora bodies) in the central nervous system. To study the pathology of LD and the functions of laforin, we disrupted the Epm2a gene in mice. At(More)
Immunogold electron microscopy has identified a variety of blood-brain barrier (BBB) proteins with transporter and regulatory functions. For example, isoforms of the glucose transporter, protein kinase C (PKC), and caveolin-1 are BBB specific. Isoform 1 of the facilitative glucose transporter family (GLUT1) is expressed solely in endothelial (and pericyte)(More)
Blood-brain barrier penetration of leucine-enkephalin, methionine-enkephalin, and other peptide-like compounds was measured after intracarotid injection of three isotopes and was found to be non-saturable over the nanomolar range of concentrations tested. No significant differences in brain regional extraction of leucine enkephalin (or morphine or heroin)(More)
Examination of blood-brain barrier (BBB) function by the intracarotid injection technique has been utilized in studies of newborn (6-30 h) and adult rabbits. The exclusion of mannitol (mol. wt. 182), dextran (mol. wt. 60,000-90,000), and indium-bound EDTA indicate that the newborn BBB has restrictive properties similar to the adult. At birth, saturable,(More)
The intracarotid injection technique has been utilized to examine blood-brain barrier function in studies of newborn (greater than 24 h), 7, 14, 21 and 28 day-old, as well as adult rabbits. The age-related modulations in blood-brain barrier transport of adenine, arginine, choline, lactate and tryptophan were defined and demonstrated to be independent of(More)
1. No evidence has been reported to date which indicates that peptides such as insulin, the enkephalins, or TRH traverse the BBB by specific transport systems. Therefore, the use of latentiated (lipid-soluble) derivatives of peptides provides the most practical approach to circumvent the restricted permeability of the BBB to peptides. In contrast to the(More)
Immunogold electron microscopy was used to examine human brain resections to localize the GLUT1 glucose transporter. The tissue examined was obtained from a patient undergoing surgery for treatment of seizures, and the capillary profiles examined had characteristics identical to those described previously for active, epileptogenic sites (confirmed by EEG(More)
Valproic acid distribution in brain is less than that of other anticonvulsants such as phenytoin or phenobarbital. Possible mechanisms for this decreased distribution space in brain include (a) increased plasma protein binding of valproate relative to the other anticonvulsants and (b) asymmetric blood-brain barrier (BBB) transport of valproate such that the(More)