Repurposing Leucovorin for Mild Traumatic Brain Injury: Evidence from Biochemical and Behavioral Outcomes in Rats

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Mild traumatic brain injury (mTBI) can cause lasting cognitive and emotional issues due to secondary injury mechanisms like oxidative stress and neuroinflammation.
• Current pharmacological treatments for mTBI's persistent effects are limited.
• Leucovorin (folinic acid), a reduced folate, is explored for repurposing as a neuroprotective agent against mTBI.

Purpose of the Study:

• To investigate the neuroprotective effects of leucovorin in an experimental model of mild traumatic brain injury (mTBI).
• To assess leucovorin's impact on behavioral deficits, oxidative stress, neuroinflammation, apoptosis, and histopathological changes post-mTBI.

Main Methods:

• Male Wistar rats underwent a modified weight-drop model of mTBI.
• Leucovorin (20 mg/kg) was administered intraperitoneally as a single dose.
• Behavioral tests (open field, elevated plus maze, forced swim, novel object recognition), biochemical assays (oxidative stress markers, inflammatory mediators, apoptosis markers, BDNF, AChE), and histopathology were performed.

Main Results:

• mTBI induced anxiety-like, depressive-like behaviors, and impaired recognition memory, alongside increased oxidative stress, inflammation, apoptosis markers, and histopathological damage.
• Leucovorin treatment significantly attenuated these biochemical and tissue alterations.
• Leucovorin administration led to improved behavioral outcomes and preserved tissue architecture, with reduced inflammatory markers.

Conclusions:

• Leucovorin demonstrated significant neuroprotective effects against behavioral, biochemical, and histopathological damage in an experimental mTBI model.
• These findings suggest leucovorin's potential as a therapeutic agent for mTBI.
• Further research is required to elucidate mechanisms, optimize treatment, and confirm clinical relevance.