Affiliations: Neuroscience Research, Research & Development,
Jesse Brown VA Medical Center Chicago, Chicago, IL, USA | Westside Institute for Science & Education
Chicago, Chicago, IL, USA | Department of Pediatrics, University of Illinois at
Chicago, Chicago, IL, USA | Department of Anatomy & Cell Biology,
University of Illinois at Chicago, Chicago, IL, USA | Department of BioEngineering, University of Illinois
at Chicago, Chicago, IL, USA
Note: [] Corresponding author: Neelima B. Chauhan, R&D (537/151),
Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL 60612, USA.
Tel.: +1 312 569 7747; Fax: +1 312 569 -8114; E-mail: nchauhan@uic.edu
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.
Keywords: Traumatic brain injury, controlled cortical impact injury, simvastatin, lovastatin, pravastatin, spontaneous exploratory working memory, learning and memory, morris water maze, Y-maze
