Activation of the Nrf2-ARE signal pathway after blast induced traumatic brain injury in mice

Area of Science:

• Neuroscience
• Cellular Biology
• Toxicology

Background:

• Blast-induced traumatic brain injury (bTBI) presents treatment challenges, with oxidative stress implicated in its pathophysiology.
• The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is known to confer protection in traumatic brain injury (TBI).

Purpose of the Study:

• To investigate the activation of the Nrf2-ARE signaling pathway in a mouse model of blast-induced TBI.
• To determine the temporal profile of Nrf2-ARE pathway activation in response to bTBI.

Main Methods:

• Mice were subjected to a modified bTBI model and assessed at various time points (6 hours to 14 days) post-injury.
• Western blot was used to quantify protein levels of nuclear Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO1).
• Real-time quantitative polymerase chain reaction and histological staining were employed to assess mRNA levels and protein localization of HO-1 and Nrf2.

Main Results:

• Significant increases in Nrf2-ARE pathway proteins (Nrf2, HO-1, NQO1) were observed in the frontal lobe by 3 days after bTBI.
• Peak mRNA levels for HO-1 and NQO1 in the frontal lobe also occurred at 3 days post-bTBI.
• Histological analysis revealed increased HO-1 expression in the frontal lobe and hippocampus, coinciding with peak nuclear Nrf2 import in the frontal lobe at 3 days.

Conclusions:

• Blast-induced TBI triggers the activation of the endogenous Nrf2-ARE signaling pathway in the brain.
• The frontal lobe exhibits peak Nrf2-ARE pathway activation approximately 3 days following bTBI.
• Targeting and activating the Nrf2 pathway represents a promising therapeutic strategy for managing bTBI.