Cathepsin B Relocalization in Late Membrane Disrupted Neurons Following Diffuse Brain Injury in Rats

Area of Science:

• Neuroscience
• Cell Biology
• Pathology

Background:

• Traumatic brain injury (TBI) causes long-term damage, but mechanisms of neuronal membrane disruption are unclear.
• Lysosomal Cathepsin B (Cath B) redistribution to the cytosol is implicated in cell death.
• Chronic effects of Cath B and membrane disruption after diffuse TBI are poorly understood.

Purpose of the Study:

• To investigate Cathepsin B (Cath B) and neuronal membrane disruption chronically after diffuse TBI.
• To assess Cath B expression, activity, and localization in relation to neuronal damage and atrophy.

Main Methods:

• Adult male Sprague-Dawley rats underwent central fluid percussion injury (CFPI).
• Western blot analysis assessed Cath B, Bak, AIF, and Bcl-xl expression and Cath B activity.
• Immunohistochemistry, quantitative image analysis, and ultrastructural verification evaluated Cath B localization.

Main Results:

• No significant differences in Cath B expression or activity were observed between sham and injured rats at any time point.
• Immunohistology revealed Cath B sub-cellular relocalization to the cytosol in membrane-disrupted neurons at 2 and 4 weeks post-injury.
• Both membrane disruption and Cath B relocalization were associated with neuronal atrophy (smaller soma and nucleus size).

Conclusions:

• Cathepsin B (Cath B) relocalizes to the cytosol in neurons with disrupted membranes weeks after diffuse TBI.
• This late-stage relocalization and membrane disruption correlate with neuronal atrophy.
• These findings suggest a potential therapeutic window for treating chronic neuronal damage following TBI.