Dissociable Long-Term Cognitive Deficits after Frontal versus Sensorimotor Cortical Contusions

Abstract

Cognitive deficits are the most enduring and disabling sequelae of human traumatic brain injury (TBI), but quantifying the magnitude, duration, and pattern of cognitive deficits produced by different types of TBI has received little emphasis in preclinical animal models. The objective of the present study was to use a battery of behavioral tests to determine if different impact sites produce different patterns of behavioral deficits and to determine how long behavioral deficits can be detected after TBI. Prior to surgery, rats were trained to criteria on delayed nonmatching to position, radial arm maze, and rotarod tasks. Rats received sham surgery (controls), midline frontal contusions (frontal TBI, 2.25 m/sec impact), or unilateral sensorimotor cortex contusions (lateral TBI, 3.22 m/sec impact) at 12 months of age and were tested throughout the next 12 months. Cognitive deficits were more robust and more enduring than sensorimotor deficits for both lateral TBI and frontal TBI groups. Lateral TBI rats exhibited transient deficits in the forelimb placing and in the rotarod test of motor/ambulatory function, but cognitive deficits were apparent throughout the 12-month postsurgery period on tests of spatial learning and memory including: (1)reacquisition of a working memory version of the radial arm maze 6-7 months post-TBI, (2) performance in water maze probe trials 8 months post-TBI, and (3) repeated acquisition of the Morris water maze 8 and 11 months post-TBI. Frontal TBI rats exhibited a different pattern of deficits, with the most robust deficits in tests of attention/orientation such as: (1) the delayed nonmatching to position task (even with no delays) 1-11 weeks post-TBI, (2) the repeated acquisition version of the water maze--especially on the first "information" trial 8 months post-TBI, (3) a test of sensorimotor neglect or inattention 8.5 months post-TBI, and (4) a DRL20 test of timing and/or sustained attention 11 months after surgery. These results suggest that long-term behavioral deficits can be detected in rodent models of TBI, that cognitive deficits seem to be more robust than sensorimotor deficits, and that different TBI impact sites produce dissociable patterns of cognitive deficits in rats.

A Comparison of the Effects of Nicotinamide and Progesterone on Functional Recovery of Cognitive Behavior following Cortical Contusion Injury in the Rat

“…4,7,24 The apparatus consisted of a circular, 183 cm diameter blue plastic pool partially filled with water (22°C) to a depth of * 41 cm. A clear plastic platform (10 cm · 10 cm) was submerged * 2 cm below the surface of the water.…”

Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat

“…The MWM has been widely utilized to assess cognitive performance following brain injury (Lindner et al, 1998, Hoane et al, 2003. A 1.5 m diameter blue fiberglass pool was filled with water (24°C) to a depth of 32 cm and a 10 cm 2 clear Plexiglas platform was submerged 1 cm below the surface of the water.…”

“…Working memory performance was tested on days 15−17 post-injury using established methods (Lindner et al, 1998, Hoane et al, 2003. The platform was submerged at the center of a new randomly chosen quadrant (south-west, north-west, and south-east) each day.…”

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

“…The previously characterized CCI injury device (Sutton et al, 1993;Lindner et al, 1998;Kelly et al, 2000) was used to generate a cortical contusion to the left hemisphere. Each animal was placed under inhalation anesthesia with isoflurane (4% for induction, 2.0% for maintenance, in 100% O 2 at 1.5 l/min).…”

“…Because oxidative stress plays an important role in neuronal injury after TBI (Shohami et al, 1997;Sullivan et al, 1998;Hall et al, 2004), we also determined if these treatments would alter oxidative stress after TBI. We employed the controlled cortical impact (CCI) model of TBI for this study, as this injury model is known to produce molecular changes and cellular damage in the hippocampus (Dash et al, 1995;Colicos et al, 1996;Oyesiku et al, 1999;McCullers et al, 2002;Saatman et al, 2006), induce hippocampal-dependent learning deficits (Hamm et al, 1992;Lindner et al, 1998;Dixon et al, 1999), and to reduce brain NE levels and turnover (Dunn-Meynell et al, 1994;Levin et al, 1995). While increased expression or production of hippocampal BDNF and synapsin I has been reported to occur after exercise in both intact rats and in rats with FPI (Timmusk et al, 1993;Neeper et al, 1996;Molteni et al, 2002;Griesbach et al, 2004bGriesbach et al, , 2007, exercise-induced effects of these markers of plasticity have not yet been evaluated in the CCI model.…”