Papaverine provides neuroprotection by suppressing neuroinflammation and apoptosis in the traumatic brain injury via RAGE- NF- B pathway

The receptor for advanced glycation end products (RAGE)- Nuclear Factor kappa B (NF-κB) signal pathway may represent a new target for the treatment of traumatic brain injury (TBI). The aim of the study is to investigate effects of papaverine on secondary signaling mechanisms through this pathway in mice TBI model.Immunohistochemically, while the number of RAGE and NF- κB positive cells, apoptotic cells increased, the number of NeuN positive cells reduced in TBI.Papaverine reduced the number of RAGE positive cells on glia and the number of NF- κB positive cells on both neuron and glia. At the same time, it decreased the number of microglia labeled with P2RY12 increased due to TBI. It also increased the NeuN positive cells and mitigated the brain edema. Results of this study showed that papaverine reduced TBI- induced neuroinflammation and apoptosis, also provided neuroprotection via the RAGE- NF-κB signal path, which is one of the possible mechanisms in TBI. [Display omitted] •The RAGE-NF-κB pathway has critical role in pathogenesis in TBI.•Papaverine showed anti-inflammatory effects via the RAGE-NF-κB pathway in TBI.•Papaverine has anti-apoptotic and neuroprotective effects in TBI.