Abstract:We previously reported a 50% reduction in cortical infarct volume following transient focal cerebral ischemia in rats preconditioned 3 days earlier with cortical spreading depression (CSD). The mechanism of the protective effect of prior CSD remains unknown. Recent studies demonstrate reversal of excitatory amino acid transporters (EAATs) to be a principal cause for elevated extracellular glutamate levels during cerebral ischemia. The present study measured the effect of CSD preconditioning on (a) intraischemic glutamate levels and (b) regulation of glutamate transporters within the ischemic cortex of the rat. Three days following either CSD or sham preconditioning, rats were subjected to 200 min of focal cerebral ischemia, and extracellular glutamate concentration was measured by in vivo microdialysis. Cortical glutamate exposure decreased 70% from 1,772.4 Ϯ 1,469.2 M-min in sham-treated (n ϭ 8) to 569.0 Ϯ 707.8 M-min in CSD-treated (n ϭ 13) rats ( p Ͻ 0.05). The effect of CSD preconditioning on glutamate transporter levels in plasma membranes (PMs) prepared from rat cerebral cortex was assessed by western blot analysis. Down-regulation of the glial glutamate transporter isoforms EAAT2 and EAAT1 from the PM fraction was observed at 1, 3, and 7 days but not at 0 or 21 days after CSD. Semiquantitative lane analysis showed a maximal decrease of 90% for EAAT2 and 50% for EAAT1 at 3 days post-CSD. The neuronal isoform EAAT3 was unaffected by CSD. This period of down-regulation coincides with the time frame reported for induced ischemic tolerance. These data are consistent with reversal of glutamate transporter function contributing to glutamate release during ischemia and suggest that down-regulation of these transporters may contribute to ischemic tolerance induced by CSD.

Genetic polymorphism of C6 in the Japanese population has been described using polyacrylamide gel isoelectric focusing electrophoresis followed by the electrophoretic blotting technique, and haplotype analysis between C6 and C7 has also been investigated. In 565 plasma samples five different common patterns and three rare variant patterns were observed, and these were controlled by autosomal codominance at a single locus with three common and one rare alleles. These alleles were designated C6*B, C6*A, C6*B2, and C6*M, and gene frequencies were estimated to be 0.50265, 0.43186, 0.06018, and 0.00531 for C6*B, C6*A, C6*B2, and C6*M, respectively. It is noteworthy that C6*B2 has a polymorphic frequency in the Japanese population. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium. Two combinations between C6 and C7 alleles, namely C6B-C7B and C6M-C7B, were shown to be in significant positive linkage disequilibrium. The presence of allelic combinations showing linkage disequilibrium suggests the close proximity between the C6 and C7 loci.

Genetic polymorphism of S-adenosylhomocysteine hydrolase (SAHH) was investigated in a total of 214 red blood cell samples from unrelated Japanese using the starch gel electrophoresis and the enzyme-specific staining procedures. Three common phenotypes were observed which corresponded to SAHH 1, SAHH 2-1, and SAHH 2, controlled by two alleles, SAHH*1 and SAHH*2. The estimated gene frequencies of SAHH*1 and SAHH*2 in Japanese were 0.953 and 0.047, respectively. This result was not different from European samples reported by Bissbort et al. (1983).

We present a 43-year-old man with cerebral air embolism that occurred during continuous drainage of infected lung bullae. This complication is extremely rare, and may have been caused by the passage of air into the pulmonary venous circulation through a bronchovenous fistula and/or damaged pulmonary vessels. Air densities were demonstrated along the right frontal gyri on a CT performed 1 h after the onset of embolism, then moved to the deep cortex after 2.5 h. Three days later, a cortical infarct accompanied with extensive white matter edema in the right frontal lobe was confirmed by MRI. These CT and MRI findings may indicate the passage of intravascular air from the superficial to the deep cortex and subsequent cerebral infarction.