Two effective behavioral tasks for evaluating sensorimotor dysfunction following traumatic brain injury in mice

Abstract

Variants of two sensorimotor tasks, the gridwalk and spontaneous forelimb use (SFL) tasks, were assessed for their ability to reveal behavioral dysfunction following traumatic brain injury (TBI) in mice. These tests have previously been used almost exclusively in evaluating models of spinal injury, ischemia and other forebrain lesions in rats. Male C57BL/6 mice were anesthetized and given unilateral parasagittal controlled cortical impact injury or sham (n=9) procedures, targeting right anterior (n=9), middle (n=9), or posterior (n=10) locations relative to bregma. Significant forelimb and hindlimb deficits contralateral to the injured hemisphere were observed for at least 1 month and 3 weeks, respectively, on the gridwalk task depending upon insult location. The SFL task revealed a significant asymmetry in forelimb use for at least 5 months following injury. These results demonstrate the effectiveness of the SFL and gridwalk tests in evaluating sensorimotor deficits in mouse injury models involving unilateral forebrain damage.

Introduction

Head injury is among the leading causes of death and disability in adults under the age of 44 (Conroy and Kraus, 1988, Kraus and McArthur, 1996). The behavioral and pathological deficits associated with traumatic brain injury (TBI) have prompted researchers to examine underlying mechanisms of trauma in search of effective treatments. In efforts to understand the trauma cascade, mouse models of injury have become increasing popular due to the ability to genetically manipulate its DNA (Longhi et al., 2001, Yakovlev et al., 2001). However, treatments that appear to be efficacious based on molecular or histopathological results may not translate into behavioral improvements. Thus, behavioral evaluation is a useful measure as it may be clinically relevant.

A wide variety of tasks have been used to evaluate sensorimotor function following TBI in the rat (Dixon et al., 1987, Hamm et al., 1994, Bramlett et al., 1995), but assessment of these deficits in mice has received far less attention. Sherbel et al. (1999) found the beam-balance task to be effective in revealing sensorimotor deficits with moderately injured mice for up to 2 weeks following insult. Deficits in rotarod performance have been observed in a moderate TBI mouse model for up to 7 days following TBI (Fox et al., 1998a, Sherbel et al., 1999), and on the beamwalk task, injured mice displayed significantly more footfaults while traversing along the beam for 28 days (Fox et al., 1998a, Fox et al., 1998b).

While the beam-balance, beamwalk and rotarod tasks have proven useful for detecting sensorimotor deficits, they focus primarily on hindlimb function (beamwalk task) or a combination of hindlimb and forelimb function (rotarod and beam-balance tasks). The gridwalk (‘footfault’) and spontaneous forelimb use (SFL) tasks offer the potential advantage of enabling the independent assessment of all four limbs and the exclusive evaluation of forelimb function, respectively. These tasks have been used with rat ischemia, spinal cord, and cortical lesion models and can be sensitive in revealing sensorimotor deficits (Hernandez and Schallert, 1988, Kunkel-Bagden et al., 1993, Z'Graggen et al., 1998, Bland et al., 2000, Schallert et al., 2000, Soblosky et al., 1997).

In this report we document the utility of the gridwalk and SFL tasks in evaluating sensorimotor dysfunction following TBI in mice. The controlled cortical impact (CCI) device was used to create the insults, due to its extensive use in mouse models of TBI (Fox et al., 1998a, Sherbel et al., 1999). Varied unilateral parasagittal injury placements were used in order to characterize the deficits resulting from injury in different neural loci.