Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

OBJECTIVE: Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats. MATERIALS AND METHODS: Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression. RESULTS: OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (p<0.05). OXC administration causes histological changes of neurocytes. OXC 281.25 mg/kg or more concentration significantly decreased neurocytes counts and increased TUNEL-staining positive neurocytes compared to Control group (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased caspase 3 activity compared to Control group in P5 rats (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased Bax, Bax/Bcl-2 ratio and cytochrome C release in frontal lobes compared to Control group in P5 rats (p<0.05). CONCLUSIONS: Oxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

Axonal degeneration induced by intraneural injection of Campylobacter jejuni antiserum containing high titer anti-GM1 antibody.

Ganglioside-like structures in CAMPYLOBACTER JEJUNI ( C. JEJUNI) lipooligosaccharide (LOS) can induce antiganglioside antibodies, which might cause nerve damage. In this study, we injected the following three antisera directly into the sciatic nerve of guinea pigs, to investigate the role of anti-glycolipids antibody in inducing neural injury: (i) the wild strain antiserum, a mixture of the sera obtained from the guinea pigs immunized with C. JEJUNI wild-type strain (HS:19) that had a high titer anti-GM1 IgG antibody (range: 800-6,400; median: 2,400) and a high titer anti-LOS IgG antibody; (ii) the GALE mutant antiserum, a mixture of the sera obtained from the guinea pigs immunized with the GALE mutant strain that had only a high titer anti-LOS IgG antibody but no anti-GM1 antibody; and (iii) the control antiserum, a mixture of the sera obtained from the guinea pigs immunized with Freund's complete adjuvant alone which had no anti-GM1 or anti-LOS IgG antibody. Pathological examinations showed that the wild strain C. JEJUNI antiserum produced axonal degeneration in sciatic nerves. Demyelination was rare, and no inflammatory cells were present. The pathological features are consistent with those seen in human patients with axonal GBS. No such changes were observed in nerves injected with the GALE mutant antiserum. The experiment showed that passive transfer of serum containing high titer GM1 antibody caused axonal degeneration of peripheral nerves. The result, which reproduced our previous findings in an active immunization study, therefore further confirmed the critical role of the anti-glycolipid antibody in the induction of neuropathy.