title: Riluzole reduces brain swelling and contusion volume in rats following controlled cortical impact injury.
abstract: Modulation of the glutamatergic and excitotoxic pathway may attenuate secondary damage following traumatic brain injury by reducing presynaptic glutamate release and blocking sodium channels in their inactivated state. The aim 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 injury). Riluzole (8 mg/kg body weight) was given 30 min, and 6, 24, and 30 h after trauma, while control rats received physiological saline. Experiments were performed at two different degrees of trauma severity as defined by penetration depth of the impactor rod (1 vs. 1.5 mm) with the aim of investigating impact of severity of tissue damage on the neuroprotective potential of riluzole. At 48 h after trauma, brains were removed to determine hemispheric swelling and water content and to assess cortical contusion volume. Before brain removal cisternal cerebrospinal fluid (CSF) was collected in all rats to determine the effects of riluzole on substances associated with edema formation. For this, the excitatory transmitter glutamate, the volume-regulatory amino acid taurine, and the ATP-degradation product hypoxanthine were analyzed by high-performance liquid chromatography. Overall, the degree of tissue damage seems to influence the neuroprotective potential of riluzole. In rats with a less severe trauma (1-mm penetration depth), hemispheric swelling, cerebral water content of the traumatized hemisphere and cortical 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 levels were significantly increased compared to nontraumatized rats (p < 0.001). However, these neurochemical parameters as measured in cisternal CSF failed 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.
authors.affiliation: Charité-Department of Neurosurgery, Berlin, Germany. john.stover@charite.de
authors.forename: J F
authors.initials: JF
authors.lastname: Stover
authors.forename: T F
authors.initials: TF
authors.lastname: Beyer
authors.forename: A W
authors.initials: AW
authors.lastname: Unterberg
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries*; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D019271:Hypoxanthine / Q000134:cerebrospinal fluid; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000627:therapeutic use*; D013654:Taurine / Q000134:cerebrospinal fluid
chemical_list: D018696:Neuroprotective Agents; D013654:Taurine; D019271:Hypoxanthine; D018698:Glutamic Acid; D019782:Riluzole