Influence of Sex and ERK MAPK on the Pressure Reactivity Index in Newborn Piglets After Fluid Percussion Injury

Greater impairment in autoregulation is seen in male versus female piglets following fluid percussion injury (FPI). This is partially mediated by a greater upregulation of extracellular signal-related kinase mitogen-activated protein kinase (ERK MAPK). We hypothesized that these trends would be reflected by the pressure reactivity index (PRx), a clinical measure of autoregulation. We further hypothesized that PRx values would correlate well with pial artery dilatory responses to hypotension. Male and female piglets were subjected to FPI and treated with a vehicle or ERK MAPK antagonist U 0126 (1 mg/kg IV) 30 min post-injury. FPI led to upregulation of CSF ERK MAPK in untreated piglets of both sexes, however significantly higher PRx values were seen in male versus female piglets. Following administration of U 0126, elevation of ERK MAPK levels was blocked in both sexes and PRx values were significantly improved in the male. A strong correlation was seen between the PRx and pial artery vasomotor activity. These data support previous observations that male piglets demonstrate reversible ERK MAPK-mediated impairment in autoregulation following FPI, which is reflected by the PRx. The strong correlation between the PRx and pial artery vasomotor activity supports the practice of continuously monitoring cerebrovascular autoregulation in patients using this index.