Neuroprotective effects of L-arginine administration after cortical impact injury in rats: dose response and time window.

ABSTRACT

Administration of L-arginine has been shown to increase cerebral blood flow and reduce neurological damage after experimental traumatic brain injury. The purpose of this study was to examine the optimal dose and time window for these neuroprotective effects. In a dose response experiment, doses of L-arginine ranging from 37.5 to 600 mg/kg were administered 5 min after a 5-m/s, 3-mm, controlled cortical impact in rats. The amount of brain injury found at 2 weeks after injury, both at the contusion site and in the ipsilateral hippocampus, were inversely related to the dose of L-arginine administered. Both 300- and 600-mg/kg doses of L-arginine significantly reduced contusion volume. The 300-mg/kg dose significantly increased the neuron density in the CA1 region of the hippocampus. Physiological effects of L-arginine were also dose-related. The greatest reduction in intracranial pressure occurred with the 300-mg/kg dose of L-arginine. Doses up to 300 mg/kg were well tolerated, but the 600-mg/kg dose resulted in transient hypotension. In another experiment, 300 mg/kg L-arginine was administered at times varying from 5 min to 48 h after injury. Contusion volume was significantly reduced when the L-arginine was given at 5 min and 1 h after injury. The protective effect was less when the same dose was given at the later times, but there was no evidence of an adverse effect even when the L-arginine was administered 48 h after injury.