Protective Effects of Aptiganel HC1 (Cerestat®) Following Controlled Cortical Impact Injury in the Rat

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Abstract
Recent studies have demonstrated a neuroprotective effect of the noncompetitive N-methyl-d-aspartate receptor antagonist aptiganel HCl (Cerestat®) in focal cerebral ischemia. In the present study, we investigated the protective ability of aptiganel HCl after controlled cortical impact injury (impact depth = 2 mm; impactor velocity = 7 mm/sec) of the left temporoparietal cortex in rats. Intravenous aptiganel HCl (2 mg/kg) or a respective volume of vehicle was injected 15 min after trauma. Animals were sacrificed 24 h after trauma. Contusion volume was measured planimetrically from hematoxylin-eosin-stained coronal slices. Hemispheric swelling and water content were determined gravimetrically. Thirty minutes before sacrifice, a Codman intracranial pressure (ICP) probe was placed in the right hemisphere, and ICP as well as mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored. Aptiganel HCl reduced contusion volume by 13.6% in treated rats (p < 0.05). Hemispheric swelling was also significantly diminished by 31.5% in accordance to a decrease in hemispheric water content (controls, 82.78 ± 0.12%, vs. aptiganel HCl, 82.30 ± 0.18%, p < 0.05). Posttraumatic ICP was not significantly lower in the aptiganel HCl treated animals (25.5 ± 2.4 mm Hg vs. 32.0 ± 2.7 mm Hg,p = 0.096). MABP was found to be higher in the treatment group 24 h after injury (107.8 ± 3.6 mm Hg vs. 89.9 ± 2.4 mm Hg, p < 0.001), resulting in a higher CPP (82.6 ± 4.2 mm Hg vs. 57.2 ± 4.6 mm Hg, p < 0.05). Taken together, aptiganel HCl exerts various beneficial effects following experimental traumatic brain injury. It decreases contusion volume and hemispheric swelling as well as water content. Thus, this drug appears promising for further clinical trials in brain trauma.