How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury

Area of Science:

• Neuroscience
• Translational Medicine
• Pharmacology

Background:

• Traumatic brain injury (TBI) involves complex, time-dependent biological responses.
• Numerous experimental TBI pharmacotherapies have failed in clinical trials, suggesting a translational gap.
• Differences in biological and pathological process timescales between rodents and humans may contribute to these failures.

Purpose of the Study:

• To compare the temporal dynamics of TBI-induced pathologies in rodent and human models.
• To identify factors contributing to the failure of translating experimental TBI treatments to clinical practice.
• To propose strategies for improving the translation of TBI research.

Main Methods:

• Comparative analysis of published data on rodent and human TBI models.
• Examination of time scales for TBI-induced changes in cerebral glucose metabolism, inflammation, axonal integrity, and water homeostasis.
• Review of limitations in current TBI research methodologies, including outcome measures and study frequency.

Main Results:

• TBI-induced pathological trajectories differ significantly between rodent and human models.
• No universal conversion rate exists between rodent and human pathophysiological processes.
• Inflammatory processes show a relatively shorter timescale in rodents compared to humans.

Conclusions:

• Species-specific differences in the timing of TBI pathologies present a major translational challenge.
• Current research methodologies and outcome measures may not adequately capture human-relevant disease progression.
• Recommendations include using clinically relevant outcome measures (e.g., in vivo imaging, proteomics) and collecting longitudinal data at higher frequencies to bridge the translational gap in TBI research.