2-PMAP Ameliorates Cerebral Vasospasm and Brain Injury after Subarachnoid Hemorrhage by Regulating Neuro-Inflammation in Rats

Abstract

A subarachnoid hemorrhage (SAH), leading to severe disability and high fatality in survivors, is a devastating disease. Neuro-inflammation, a critical mechanism of cerebral vasospasm and brain injury from SAH, is tightly related to prognoses. Interestingly, studies indicate that 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) crosses the blood–brain barrier easily. Here, we investigated whether the vasodilatory and neuroprotective roles of 2-PMAP were observed in SAH rats. Rats were assigned to three groups: sham, SAH and SAH+2-PMAP. SAHs were induced by a cisterna magna injection. In the SAH+2-PMAP group, 5 mg/kg 2-PMAP was injected into the subarachnoid space before SAH induction. The administration of 2-PMAP markedly ameliorated cerebral vasospasm and decreased endothelial apoptosis 48 h after SAH. Meanwhile, 2-PMAP decreased the severity of neurological impairments and neuronal apoptosis after SAH. Furthermore, 2-PMAP decreased the activation of microglia and astrocytes, expressions of TLR-4 and p-NF-κB, inflammatory markers (TNF-α, IL-1β and IL-6) and reactive oxygen species. This study is the first to confirm that 2-PMAP has vasodilatory and neuroprotective effects in a rat model of SAH. Taken together, the experimental results indicate that 2-PMAP treatment attenuates neuro-inflammation, oxidative stress and cerebral vasospasm, in addition to ameliorating neurological deficits, and that these attenuating and ameliorating effects are conferred through the TLR-4/NF-κB pathway.