Ginseng extract attenuates early MRI changes after status epilepticus and decreases subsequent reduction of hippocampal volume in the rat brain.

Prolonged epileptic seizures during status epilepticus (SE) are known to cause neuronal death and lead to brain damage. Lesions in various brain regions can result in memory and cognitive impairment, thus searching of new neuroprotective drugs is important. We evaluated effects of single and chronic administration of ginseng extract on early and late changes in MRI measurements in the rat brain after lithium-pilocarpine SE. Butanol extract of ginseng root cell culture DAN-25 was administered after termination of SE. MRI study of the rat brain was performed 2, 7, and 30 days after SE. High-resolution T2-weighed images and T2-maps were obtained, and total damaged area, hippocampal volume, and T2 relaxation time in several brain structures were calculated. Single administration of ginseng extract attenuated early changes in brain structures found on day 2 after SE. Both single and chronic treatment with ginseng extract decreased brain damage on day 7 after SE. An increase in T2-relaxation time in the hippocampus on day 2 after SE was less prominent in ginseng-treated rats than in saline-treated rats. 30 days after SE, the reduction of hippocampal volume was found both in saline-treated and ginseng-treated rats; however, it was less pronounced in ginseng-treated rats. We conclude that administration of ginseng extract after SE termination reduced brain damage caused by prolonged seizures. Ginseng extract was effective during early period after SE and had a specific protective effect on the hippocampus.

Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: influence of the formulation parameters.

Poly(lactide-co-glycolide) (PLGA) nanoparticles coated with poloxamer 188 (Pluronic((R)) F-68) or polysorbate 80 (Tween((R)) 80) enable an efficient brain delivery of the drugs after intravenous injection. This ability was evidenced by two different pharmacological test systems employing as model drugs the anti-tumour antibiotic doxorubicin and the agonist of opioid receptors loperamide, which being P-gp substrates can cross the blood-brain barrier (BBB) only in pharmacologically insignificant amounts: binding of doxorubicin to the surfactant-coated PLGA nanoparticles, however, enabled a high anti-tumour effect against an intracranial 101/8 glioblastoma in rats, and the penetration of nanoparticle-bound loperamide into the brain was demonstrated by the induction of central analgesic effects in mice. Both pharmacological tests could demonstrate that therapeutic amounts of the drugs were delivered to the sites of action in the brain and showed the high efficiency of the surfactant-coated PLGA nanoparticles for brain delivery. The results of the study also demonstrated that the efficacy of brain delivery by nanoparticles not only is influenced by the coating surfactants but also by other formulation parameters such as core polymer, drug, and stabilizer.

Absence seizures during pregnancy in WAG/Rij rats.

Spontaneously occurring spike-wave discharges (SWDs) and serum concentrations of ovarian steroid hormones were investigated before, during and after pregnancy in WAG/Rij rats, a rat strain with genetically determined absence seizures. Eight groups of rats were included in the assays of progesterone and estradiol: rats at diestrus, at various days of pregnancy and at lactating days. The number of SWDs in cortical EEG of WAG/Rij rats was decreased from the 3rd up to the 18th day of pregnancy and subsequently increased to control level. Thereafter, a new decrease was found 2-3 days after parturition. Serum concentration of progesterone was threefold increased at the 3rd day of pregnancy, remained elevated until the 18th day of pregnancy and returned to control values before delivery. Over measured days, estradiol was significantly elevated only at the 18th day of pregnancy. Results demonstrate that physiological conditions induced by the state of pregnancy lead to suppression of occurrence of SWDs. Changes in plasma progesterone concentration correspond to the changes in number of SWDs: an increased level of progesterone during pregnancy is accompanied by a decreased number of SWDs, while a decrease in circulating progesterone before parturition is paralleled by an increase of SWDs. Of interest, the relationship between SWDs and concentration of progesterone found during pregnancy is diametrically opposite to results obtained in acute administration studies of progesterone in nonpregnant animals.