gms | German Medical Science

Objective: The Sulfonylurea receptor 1 (SUR1) regulates non-selective cation channels in ischemic astrocytes, neurons and endothelial cells. Blocking of SUR1 with low-dose glibenclamide reduces cerebral edema, infarct volume and mortality rate in models of experimental cerebral stroke and subarachnoid hemorrhage. In this current study we investigated the effect of glibenclamide on the development of secondary brain damage after experimental traumatic brain injury (TBI) in rats.

Method: Experimental TBI was performed by controlled cortical impact injury (CCI). Sprague-Dawley rats divided into three groups were randomized to glibenclamide or vehicle treatment that was administered as a subcutaneous bolus 15 minutes after trauma and via Alzet micro-pumps over 7 days. In group 1 (n = 20) acute (patho-) physiological changes (MAP, HR, ICP) over 180 minutes following CCI were examined. In group 2 (n = 35) brain water content was assessed gravimetrically 24 h after CCI, and in group 3 (n = 20) contusion volume depicted by MRI scans and neurological function were quantified 8 h, 48 h, 72 h and 7 d following CCI.

Results: Instantaneously after CCI ICP increased significantly in comparison to baseline levels, but as well as MAP and HF no significant differences between the treatment and control groups could be detected during the acute stage. 24 hours after TBI, however, brain water content reflecting brain edema was reduced significantly in rats treated with glibenclamide compared to controls (80.3 ± 0.3% vs. 80.8 ± 0.4%, p < 0.01). Contusion volumes increased continuously within the first 72 hours and diminished 7 days after CCI. Due to the administration of glibenclamide contusion volume could be decreased significantly at each point in time (8 h: 158.0 mm³ ± 36.8 mm³ vs. 268.0 mm³ ± 42.6 mm³, p < 0.001; 24 h: 172.5 mm³ ± 38.7 mm³ vs. 298.3 mm³ ± 60.4 mm³, p < 0.001; 72 h: 211.1 mm³ ± 41.0 mm³ vs. 311.6 mm³ ± 61.0 mm³, p < 0.001; 7 d: 107.5 mm³ ± 20.1 mm³ vs. 173.6 mm³ ± 40.9 mm³, p < 0.001). Neurological function of the first 7 days following CCI, however, was not influenced by the treatment.

Conclusions: In summary, treatment with glibenclamide reduces brain edema and contusion volume after CCI and thus might offer a promising treatment option for patients with TBI.