Injury & Pain – Traumatic Brain Injury
Traumatic brain injury (TBI) is defined as damage to the brain resulting from mechanical force, which may include impact, rapid acceleration or deceleration, blast, or penetration, by a projectile. The most common causes of TBI include falls, sports injury and transportation accidents. In the US, falls account for 28% of TBI, motor vehicle (MV) accidents for 20%, being struck by an object for 19%, and non-motor vehicle accidents for 3%. To replicate injuries in humans, several animal models of TBI have been developed out of which an injury at the cortical level by a mechanical trauma by controlled cortical impact (CCI) is the widely used animal model in rats and has very well characterized and published. Different behavioral assessments, including motor, sensory and cognition are used to characterize the level of injury in this model, and serves as an important tool for evaluating the therapeutic efficacy of various drugs indicated for TBI.
Cognitive Assessments
Spontaneous Alternation Test (SAT)
The spontaneous alternation test is used to assess spatial working memory. In this test, a plus-shaped maze was used. Four identical arms extend from a central platform. Rats were allowed to navigate in the maze freely for 12 min and the number and sequence of entries were recorded. An alternation is defined as entry into four different arms on overlapping sets of five consecutive arm entries. A percent alternation score is calculated as the ratio of actual alternations divided by maximum possible alternations x 100.
Any drug treatment which may increase the alternation score may be considered beneficial. Progesterone 16mg/kg initiated i.p. 1 h after injury and continued s.c. daily for 5 days improved the SAT scores
Beneficial effect of Progesterone (PR) treatment on the spontaneous alternations after injury, assessed by the SAT: Deficits in cognition after CCI were significantly reversed by PR (16 mg/kg)-treatment compared with the control. Significant differences were not detected with lower doses. Error bars indicate SEM; *p<0.05, n=10 animals per group
Morris Water Maze (MWM) Test
The MWM test is used to assess hippocampal-dependent spatial learning and memory. In MWM there is a submerged platform located in one of four quadrants in a large, water- filled pool. The rats use extra-maze cues to locate the position of a platform over a series of trials. Over the course of several days rodents learn to find the hidden platform in order to escape from the water (acquisition). CCI rats showed deficits as compared to sham rats in this test as seen by an increase in the latency to find the hidden platform. Any drug treatment which may decrease the latency to find the platform may be considered beneficial. Progesterone (16 mg/kg) initiated i.p. 1 h after injury and continued s.c. for daily for 5 days significantly decreased the latency to reach platform.
Beneficial effect of progesterone (PR) treatment on the latency to reach a hidden platform after injury, assessed by the MWM tests: Deficits in cognition after CCI were significantly reversed by PR (16 mg/kg)-treatment compared with the control. Significant differences were not detected with lower doses. Error bars indicate SEM; *p<0.05, n=10 animals per group
