Glibenclamide reduces secondary brain damage after experimental traumatic brain injury

• Glibenclamide reduced brain edema by 15% 24 h after CCI injury in rats.
• Glibenclamide diminished contusion volumes assessed by MRI imaging (8 h–7 d post CCI).
• Glibenclamide-treated rats showed reduced number and duration of epileptic seizures.
• Mikrodialyses showed a positive correlation between glutamate and epileptic seizures.

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI.Anesthetized adult Sprague–Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15 min after CCI injury and continuously via osmotic pumps throughout 7 days. In an acute trial (180 min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24 h after CCI injury and contusion volumes were measured by MRI scanning technique at 8 h, 24 h, 72 h, and 7 d post injury. Throughout the entire time of observation neurological function was quantified using the “beam-walking” test.Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47% ± 0.37% (glibenclamide) vs. 80.83% ± 0.44% (control); p < 0.05; n = 14). Contusion sizes increased continuously within 72 h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53 ± 38.74 mm3 (glibenclamide) vs. 299.20 ± 64.02 mm3 (control) (p < 0.01; n = 10; 24 h) or 211.10 ± 41.03 mm3 (glibenclamide) vs. 309.76 ± 19.45 mm3 (control) (p < 0.05; n = 10; 72 h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3–6 h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7 days.In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI.