gms | German Medical Science

Objective: In addition to dopaminergic, serotonergic and adrenergic effects Lisuride is a potent antiinflammatory and antioxidative agent. The aim of this study was to examine if Lisuride can influence the appearance of early posttraumatic seizures and the development of secondary brain damage after Controlled Cortical Impact injury (CCII) in rats.

Methods: 70 male Sprague-Dawley rats (350-400g) were anesthetized with isoflurane and N₂O and a CCI injury (CCII: 7m/s, contact time 300ms, velocity 1.5mm) was performed. 30 minutes after trauma either Lisuride (s.c. bolus:0.3mg/kg BW) or same amounts of physiological NaCl solution were applied as a subcutaneous bolus. In group A (n=18) anesthesia was maintained over 3 hours and MAP, ICP and EEG were digitally recorded. The EEG was analyzed by a blinded investigator. In group B (n=20) osmotic pumps (Alzet^®, 2ML1, 0,5 mg/kg/d) were implanted additionally and contusion volume was assessed via T2 weighted MRI scans 8h, 24h, 72h and 7d after CCII. Functional outcome was judged by a Comprehensive Neuroscore. In group C (n=32) osmotic pumps were implanted subcutaneously and animals were sacrified 24h after CCII and 30 minutes after infusion of 2% Evans Blue (EB 2 ml/kgBW). Brain water content was quantified gravimetrically. Differences were found significant if p<0.05.

Results: After trauma EEG activity was reduced significantly without change in the mean frequency. In each group, 6 animals (67%) showed epileptiform discharges. In the verum treated group the absolute number and duration of seizures was reduced (10 vs. 19 respektively 300±100 vs. 100±75s, p<0.1). These were limited to the first 10 minutes after drug treatment. In group C a trend for a decrease in brain water content and EB extravasation was found but there was no difference in contusion volume and Comprehensive Neuroscores (B). Unexpectedly a significant reduction of MAP and CPP was observed directly after injection of Lisuride (MAP: 85±15 mmHg vs. 68±8 mmHg, 60 min. post CCI, p<0.01).

Conclusions: Although Lisuride caused hypotension in the acute phase after CCII, secondary contusion volumes did not increase. This may be due to its antiepileptic properties and reduced brain swelling. It appears that Lisuride has neuroprotective effects and could be a promising substance in the treatment of traumatic brain injury. However, a different dosage needs to be established to avoid hypotension in future studies.