Cellular damage markers in the temporal lobe of a patient with Dyke-Davidoff-Masson Syndrome.

We studied the cellular damage in a patient with Dyke-Davidoff-Masson Syndrome and a history of chronic temporal lobe epilepsy resistant to treatment. The epileptogenic zone was localized to the right temporal lobe, and an extensive surgical removal of the temporal neocortex plus amygdala and hippocampus was performed. The specimens were immediately frozen in liquid nitrogen and stored at -75 degrees C for biochemical studies. Specimens were immersed and fixed in freshly prepared 4% paraformaldehyde for histopathological evaluation. Neurotransmitter levels were highest in the hippocampus compared to the temporal neocortex (T1, T2, and T3). In the amygdala, GABA was found whereas other amino acids were absent. We found marked dislamination in all areas of the cortex, neuronal loss, amylaceous bodies, and neuronal cytomegaly with cytoskeletal disorganization containing dense fibrillar cytoplasmic aggregates, nodular heterotopias, dysplastic and large neurons with high Nissl staining, intermixed with balloon cells with atypical nuclei, often with binucleation, and abundant glassy eosinophilic cytoplasm. Positive immunoreactive cells with nestin, vimentin, and enhanced expression of astrocytes were observed in all brain regions. This patient's syndrome should be considered as a postinfectious/post-stroke event that caused hemiparesis and later recurrent seizures. Higher expression of nestin and vimentin has been observed in proliferative neuronal cells, the expression in astrocytes may mainly reflect an early response of these cells to injury. Nestin may play a role in protecting the brain from injury. It has been proposed that re-expression of embryonic genes by mature cells is associated with morphological plasticity.

Quinolinic acid induces oxidative stress in rat brain synaptosomes.

The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

Quinolinic acid neurotoxicity: in vivo increased copper and manganese content in rat corpus striatum after quinolinate intrastriatal injection.

Copper and manganese, two essential metals involved in physiological and physiopathological processes in the brain, were measured in corpora striata of rats 7 days after intrastriatal injection of quinolinic acid (QUIN, 240 nmol/l microliters), an N-methyl-D-aspartate (NMDA) receptor agonist with toxic activity. Seven days after QUIN administration, copper and manganese contents were assessed by graphite furnace atomic absorption spectrophotometry. Total copper content was increased by 152% in QUIN-treated rats (18.74 +/- 2.05 micrograms/g) as compared to control animals (7.44 +/- 1.15 micrograms/g), whereas manganese striatal levels were enhanced by 35% (0.30 +/- 0.02 microgram/g) vs. control values (0.22 +/- 0.02 microgram/g). Quinolinate-induced striatal increase in copper and manganese levels were prevented by 23% (9.18 +/- 1.43 micrograms/g) and -0.45% (0.22 +/- 0.03 microgram/g) vs. control values, respectively, in rats pretreated with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), 60 min before QUIN administration. As an index of QUIN neurotoxicity, striatal GABA levels were also measured 7 days after QUIN injection. GABA content was decreased by-55% in QUIN-lesioned rats (96.37 +/- 8.92 micrograms/g), whereas MK-801 was able to block QUIN-induced GABA depletion by 2% (219.37 +/- 10.60) vs. control values (214.2 +/- 21.88 micrograms/g). These findings suggest that increased concentrations of transition metals can be mediated by selective overactivation of NMDA receptors and might be a consequence of neural loss as well as glial response to damage.

Thallium increases monoamine oxidase activity and serotonin turnover rate in rat brain regions.

The effect of thallium acetate administration on monoaminergic pathways was studied in male Wistar rats using 30 mg/kg and 50 mg/kg acute IP doses. We found that thallium activated both monoamine oxidase (MAO) activity and serotonin turnover rate in rat brain regions, that may contribute to the neuronal damage mechanism of the agent. MAO activity in midbrain and pons was increased at both doses (at 30 mg/kg dose by 27.7% and 37%; at 50 mg/kg dose by 48% and 47%, respectively vs. control group). Serotonin turnover rate in pons was also increased at the 30 mg/kg dose (172%) while midbrain and pons serotonin turnover was increased only at the 50 mg/kg dose (56% and 166%, respectively vs. control group). Dopamine turnover rate was not significantly changed. The results indicate that thallium induced a significant increase in pons and midbrain MAO activity and also in serotonin turnover rate as compared with control animals, and this could led to behavioral and toxic alterations in the rats intoxicated with thallium.

Dapsone attenuates kainic acid-induced seizures in rats.

We tested the ability of dapsone (4,4'-diamino-diphenyl sulfone) to attenuate kainic acid-induced seizures. We observed that 9.375 and 12.5 mg/kg doses of dapsone administered 30 min before a single kainic acid (10 mg/kg) i.p. injection were able to decrease the time of electroencephalographic seizures by 52% and 82%, respectively, as compared with rats administered with 10 mg/kg kainic acid only. The 12.5 mg/kg dose of dapsone was also able to diminish both kainic acid-evoked body and head shakes (58%) and kainic acid-induced mortality (75%). These results suggest that dapsone could be used in clinical trials as anticonvulsant.