Abstract
Purpose: Traumatic brain injury (TBI) is a global health concern and growing socio-economic burden with limited treatment options. Behavioral assessment in experimental TBI with candidate therapeutic interventions is critical in order to expedite clinical translation. Statins constitute one of the potential treatment options based on their proven beneficial effects in various models of neurotrauma. We compared functional outcome after dietary intervention with representative hydrophilic Pravastatin or lipophilic Simvastatin and Lovastatin to test if different statins will differentially affect cognitive outcomes after injury in a controlled cortical impact injury (CCI) mouse model of TBI.
Methods: Mice were subjected to TBI with a controlled cortical impact produced on the left somatosensory-parietal cortex between bregma −1.82 and −2.06, fed with Simvastatin/Lovastatin/Pravastatin (2 mg/kg) for 8 weeks, evaluated for learning, memory and spontaneous exploration behavior followed by immunocytochemistry of an axonal marker.
Results: Results indicate that feeding of TBI mice with Simvastatin and Lovastatin significantly improved spatial learning and memory, restored spontaneous exploration and restored axonal integrity (Simvastatin > Lovastatin). On the other hand, Pravastatin failed to improve spatial learning or memory or exploration or axonal damage.
Conclusions: Current findings confirm maximum benefits rendered by Simvastatin and reinforce Simvastatin as the candidate therapy for treating TBI.
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