Comparison of Tetrahydrobiopterin and L-Arginine on Cerebral Blood Flow after Controlled Cortical Impact Injury in Rats

Abstract

The purpose of this study was to compare the effects of L-arginine and tetrahydrobiopterin administration on post-traumatic cerebral blood flow (CBF) and tissue levels of NO in injured brain tissue. Rats were anesthetized with isoflurane. Mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations were measured prior to, and for 2 h after a controlled cortical impact injury. L-Arginine, 300 mg/kg, tetrahydrobiopterin, 10 mg/kg, or equal volume of saline was given at 5 min after injury. In the saline-treated animals, LDF decreased to 34 ± 4% of baseline values after injury. NO concentration also decreased by approximately 20 pmol/ml from baseline values. L-Arginine and tetrahydrobiopterin administration both resulted in a significant preservation of tissue NO concentrations and an improvement in LDF, compared to control animals given saline. These studies demonstrate that tetrahydrobiopterin administration has a beneficial effect on cerebral blood flow that is similar to L-arginine administration, and may suggest that depletion of tetrahydrobiopterin plays a role in the post-traumatic hypoperfusion of the brain.