The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury

The aim of this study is to investigate whether the neuroprotective effect of AMN082 is via attenuating glutamic receptor associated neuronal apoptosis and improves functional outcomes after traumatic brain injury (TBI). Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 was intraperitoneally injected (10 mg/kg) at 0, 24, and 48 hr after TBI. During the 120 minutes after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. The motor function, infarction volume, and neuronal nitrosative stress-associated apoptosis, N-Methyl-D-aspartate receptor 2A (NR2A) and NR2B expression were measured on the 3rd day after TBI. The results showed AMN082-treated group had the lower ICP and higher CPP after TBI. The TBI-induced motor deficits, increased infarction volume, neuronal apoptosis, 3-nitrotyrosine and inducible nitric oxide synthase expression in the peri-contusion cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased the NR2A and NR2B expression in neuronal cells. We concluded intraperitoneal injection of AMN082 for 3 days may ameliorate TBI insults by attenuating glutamic receptor associated nitrosative stress and neuronal apoptosis in the peri-contusion cortex. We suggest AMN082 administration in acute stage may be a promising strategy for TBI.