Johana Bastidas, Michael Lang, Rachel Barrett, Smriti Mongia, Daniel Havas, Taleen Hanania.
Traumatic brain injury (TBI) is a major cause of death and disability. There is currently no effective
treatment for TBI, and survivors suffer from a variety of long-lasting health consequences.
Pioglitazone, Amantadine and Glibenclamide have showed promising results in improving
locomotor, cognition, and/or histology outcomes in different preclinical models of TBI. In this
study, we compared the efficacy of these 3 compounds in a well-established model of TBI in male
Sprague Dawley rats.
The Controlled cortical impact (CCI) model uses an electromagnetically piston to induce
reproducible injuries that result in consistent changes in locomotion and cognition. Immediately
after CCI, animals received either: Pioglitazone (20mg/kg, PO, for 14 days); Glibenclamide (initial
dose of 10μg/Kg, IP. Followed by 0.2μg/hour using a SC minipump); Amantadine (20mg/Kg, IP,
for 14 days) or Saline (5ml/Kg, IP, for 14 days). Locomotor changes were evaluated at 3, 5 and 7
days after TBI using the Beam-Balance test, and at 7 and 22 days after TBI using the Paw-
Placement preference test and Gait analysis. Cognition changes were evaluated starting at day
14 after TBI using the Morris Water Maze test. Finally, lesion size volume and inflammatory
markers were evaluated in brain tissue sample.
Rats receiving Pioglitazone (an FDA approved drug for diabetes) presented significant
improvement in locomotor performance (Beam-Balance test at 3 and 5 days, p>0.01; and paw
placement preference test, p>0.05). Animals treated with Glibenclamide and Amantadine did not
show any significant improvement in behavior outcomes. Behavioral changes are correlated with
Lesion measurements and inflammation markers.