Sustained deficiency of mitochondrial complex I activity during long periods of survival after seizures induced in immature rats by homocysteic acid.

Our previous work demonstrated the marked decrease of mitochondrial complex I activity in the cerebral cortex of immature rats during the acute phase of seizures induced by bilateral intracerebroventricular infusion of dl-homocysteic acid (600 nmol/side) and at short time following these seizures. The present study demonstrates that the marked decrease ( approximately 60%) of mitochondrial complex I activity persists during the long periods of survival, up to 5 weeks, following these seizures, i.e.

Isolation of plasma membrane compartments from rat brain cortex; detection of agonist-stimulated G protein activity.

Background: Heterotrimeric guanine nucleotide-binding proteins (G proteins) play an essential role in linking cell-surface receptors to effector proteins at the plasma membrane. The functional activities of G proteins in various plasma membrane compartments remain to be elucidated.

Material/methods: Plasma membranes from rat cerebral cortex were isolated on Percoll and fractionated by sucrose-density gradient.

Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures.

The major finding of the present study concerns the marked decrease of respiratory chain complex I activity in the cerebral cortex of immature rats following seizures induced by bilateral intracerebroventricular infusion of dl-homocysteic acid (600 nmol/side). This decrease was already evident during the acute phase of seizures (60-90 min after infusion) and persisted for at least 20 h after the seizures. It was selective for complex I since activities of complex II and IV and citrate synthase remained unaffected.

Quinolinic acid induces NMDA receptor-mediated lipid peroxidation in rat brain microvessels.

Quinolinic acid increased the generation of lipid peroxidation products by isolated rat brain microvessels in vitro. The effect was inhibited both by a specific NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid and by reduced glutathione (GSH). Furthermore, quinolinic acid displaced specific binding of [(3)H]-L-glutamate by cerebral microvessel membranes, particularly in the presence of NMDA receptor co-agonist (glycine) and modulator (spermidine).

Main subunits of ionotropic glutamate receptors are expressed in isolated rat brain microvessels.

Excitatory amino acids are known to modulate blood-brain barrier (BBB) permeability, however, the information on glutamate receptors in cerebral capillaries is inconsistent. In the present study, freshly isolated microvessels obtained from saline-perfused rat brains were used. Gene expression of the main N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor subunits NMDAR1 and GLUR1, respectively, were investigated by reverse transcription-polymerase chain reaction (RT-PCR).