Efficacy of dapsone administered alone or in combination with diazepam to inhibit status epilepticus in rats.

Status epilepticus (SE) is a serious medical condition, as it may trigger epileptogenesis. SE produces continuous generalized seizures resulting in irreversible brain damage. Therefore, the use of neuroprotective agents to prevent cell damage, may reduce the impact of SE. The use of diazepam (DZP), has shown limited neuroprotective effect in SE patients. According to previous reports, dapsone (DDS) is able to reduce both cell damage and seizures, when administered 30 min before the onset of seizures. This study is aimed to evaluate the ability of DDS, alone or in combination with DZP starting their administration once the SE is onset to evaluate the control of seizures in rats. Results showed a reduced convulsive electrical activity after 30 min, 1 and 2 h after SE induced by kainic acid (KA) administration, in the animals treated with DZP alone or in combination with DDS. At 24 h, we observed electrical activity similar to baseline in all groups receiving treatment. The animals treated with DDS and DZP alone or in combination showed an increase in the number of viable pyramidal cells but only the combination showed a lower number of damaged pyramidal neurons of hippocampal CA3. In conclusion, DDS plus DZP was able to control SE and to prevent SE-induced damage, when administered in combination with DZP. As DDS is already in use for patients with leprosy, that combination may be a safe, good option for human cases of SE.

Protective effect of dapsone on cognitive impairment induced by propofol involves hippocampal autophagy.

Post-operative cognitive dysfunction (POCD) is a commonly seen postoperative complication in elderly patients and its underlying mechanisms are still unclear. Autophagy, a degradation mechanism of cellular components, is required for cell survival and many physiological processes. Although propofol is one of the most commonly used intravenous anesthetics, investigations into its mechanisms and effects on cognition in aged rodents are relatively scarce. In this study, we evaluate the influence of propofol on learning and memory, and identify the potential role of hippocampal autophagy in propofol-induced cognitive alterations in aged rats. The results demonstrate that 4h propofol exposure significantly impaired cognitive performance through the inhibition of hippocampal autophagy. Diaminodiphenyl sulfone (dapsone, DDS), which was used as an anti-leprosy drug, has been found to have neuroprotective effects. We have previously demonstrated that DDS can improve surgical stress induced depression- and anxiety-like behavior. We therefore aimed to investigate the effects of DDS on propofol-induced cognitive dysfunction and associated hippocampal autophagy responses. Pretreatment with 5mg/kg or 10mg/kg body weight DDS significantly improved the behavioral disorder and upregulated the inhibited autophagic response in aged rats. Our exploration is the first to establish an in vivo link between central autophagy and cognitive dysfunction in aged hippocampus after propofol anesthesia and demonstrate that the prophylactic effect of DDS on the cognitive impairment induced by propofol involves autophagy. These findings may imply a potential novel target for the treatment in patients with propofol anesthesia-induced cognitive impairment.

Comparing the anticonvulsive effects of dapsone on amygdala-kindled seizures and hippocampal-kindled seizures in rats.

Dapsone, an antileprosy drug, was administered to rats with amygdala (AM)-kindled seizures or hippocampal (HIPP)-kindled seizures to elucidate its anticonvulsive efficacy. Adult male Wistar rats were subjected to kindling stimulations 2 weeks after electrode-implantation. The subjects were tested once a day for 7 successive days after inducing three generalized (stage 5) seizures to study the effects of dapsone. Dapsone had an inhibitory effect on stage 5 seizures at 12.50 mg/kg in the AM-kindled rats and at 6.25 mg/kg and 9.375 mg/kg in the HIPP-kindled rats. Thus, there was a distinct difference in the effective dose for generalized seizures between the AM-kindled rats and the HIPP-kindled rats. The inhibitory action of dapsone on stage 5 seizures may be due mainly to the elevation of the afterdischarge-triggering threshold at the stimulation site of the AM or HIPP. Such inhibitory action appears prominently at serum concentrations of about 13 micrograms/ml in AM-kindled rats and about 6 micrograms/ml in HIPP-kindled rats. The level of 6 micrograms/ml almost equals the therapeutic serum concentration of dapsone used in the treatment of leprosy.