Neonatal pyridoxine administration long lastingly accelerates cortical spreading depression in male rats, without affecting anxiety-like behavior

Abstract

ABSTRACT Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD). Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session). Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed. Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing.