Aminoguanidine reverses cognitive deficits and activation of cAMP/CREB/BDNF pathway in mouse hippocampus after traumatic brain injury (TBI)

ABSTRACTPrimary Objective: We aim to study the effects of chronic aminoguanidine (AG) administration on learning and memory impairment after TBI and explore the potential mechanism involved in this process.Research Design: Male C57BL/6J mice were divided into 6 groups: Control, TBI + Veh, TBI+ AG (50, 100, 200 and 400 mg/kg, i.p.).Methods and Procedures: Then, we measured cyclicadenosine 3ʹ, 5ʹ-monophosphate (cAMP) content, phosphorylated form of cAMP-response element binding protein (p-CREB) level, iNOS, brain-derived neurotrophic factor (BDNF) and postsynaptic density-93/95 (PSD-93/95) expression in hippocampus. The learning and memory abilities were assessed using Morris water maze and step-down test.Main Outcomes and Results: The results demonstrate that TBI induced down-regulation of BDNF, loss of PSD-93/95, learning and memory deficits with down-regulation of cAMP content and p-CREB/CREB ratio. Administration of AG (200 and 400 mg/kg) reversed TBI induced down-regulation of BDNF and PSD-93/95, up-re...