Riluzole reduces brain swelling and contusion volume in rats following controlled cortical impact injury

Modulation of the glutamatergic and excitotoxic pathway may attenuate secon dary damage following traumatic brain injury by reducing presynaptic glutam ate release and blocking sodium channels in their inactivated state. The ai m of the present study was to investigate the neuroprotective potential of riluzole in traumatic brain-injured rats. A left temporoparietal contusion was induced in 70 male Sprague-Dawley rats (controlled cortical impact inju ry). Riluzole (8 mg/kg body weight) was given 30 min, and 6, 24, and 30 h a fter trauma, while control rats received physiological saline. Experiments were performed at two different degrees of trauma severity as defined by pe netration depth of the impactor rod (1 vs. 1.5 mm) with the aim of investig ating impact of severity of tissue damage on the neuroprotective potential of riluzole. At 48 h after trauma, brains were removed to determine hemisph eric swelling and water content and to assess cortical contusion volume. Be fore brain removal cisternal cerebrospinal fluid (CSF) was collected in all rats to determine the effects of riluzole on substances associated with ed ema formation. For this, the excitatory transmitter glutamate, the volume-r egulatory amino acid taurine, and the ATP-degradation product hypoxanthine were analyzed by high-performance liquid chromatography. Overall, the degre e of tissue damage seems to influence the neuroprotective potential of rilu zole. In rats with a less severe trauma (l-mm penetration depth), hemispher ic swelling, cerebral water content of the traumatized hemisphere and corti cal contusion volume were significantly reduced under riluzole compared to controls (p < 0.05). In rats with a more severe trauma (1.5-mm penetration depth), the neuroprotective effect of riluzole failed to reach statistical significance. Following trauma, CSF glutamate, taurine, and hypoxanthine le vels were significantly increased compared to nontraumatized rats (p < 0.00 1). However, these neurochemical parameters as measured in cisternal CSF fa iled to reflect trauma-dependent increases in severity of tissue damage and did not reveal riluzole-mediated neuroprotection. Under the present study design, riluzole significantly reduced brain edema formation and contusion volume in rats subjected to a mild focal cortical contusion.