Sex and Age Differences in Epinephrine Mechanisms and Outcomes after Brain Injury

Area of Science:

• Neuroscience
• Pediatric Traumatology
• Pharmacology

Background:

• Traumatic brain injury (TBI) is a leading cause of death in children, with specific age and sex groups experiencing worse outcomes.
• Impaired cerebral autoregulation and histopathology are significant contributors to poor outcomes following TBI.
• The role of c-Jun-terminal kinase (JNK) in TBI-related histopathology is not well understood.

Purpose of the Study:

• To investigate the age- and sex-dependent protective effects of epinephrine (EPI) on cerebral autoregulation and TBI-induced histopathology.
• To determine the involvement of JNK signaling in the outcomes of TBI treated with EPI.

Main Methods:

• Lateral fluid percussion injury (FPI) was induced in anesthetized pigs.
• Pial artery reactivity was assessed using a closed cranial window.
• Phosphorylated JNK MAPK levels were quantified using enzyme-linked immunosorbent assay (ELISA).

Main Results:

• Epinephrine (EPI) preserved cerebral autoregulation and prevented histopathology in newborn males and females, and in juvenile females after TBI.
• EPI treatment blocked the upregulation of phosphorylated JNK MAPK in these protected groups.
• Juvenile males did not show the same protective effects from EPI treatment.

Conclusions:

• Epinephrine (EPI) demonstrates age- and sex-dependent neuroprotective effects following traumatic brain injury (TBI).
• The protective mechanisms of EPI involve preserving cerebral autoregulation and limiting histopathology.
• EPI exerts its beneficial effects through the blockade of JNK signaling pathways.