A simple, efficient tool for assessment of mice after unilateral cortex injury
Introduction
Traumatic brain injury (TBI) remains a serious clinical problem associated with high mortality and lingering socioeconomic consequences (Thurman and Guerrero, 1999). In the course of investigating the neuropathology and functional deficits caused by TBI, a number of rodent models have been developed. Recently, reproducible mouse models of TBI (Leker et al., 2002, Smith et al., 1995, Statler et al., 2001) have increased the utility of transgenic manipulations to assess the contribution of specific genes to injury and recovery. Such assessment requires the accurate evaluation of neurological function in mice.
Most neurological tests used in TBI mice are adapted from those developed for rats (Fujimoto et al., 2004, McIntosh et al., 1989) or uninjured mice (Crawley, 2000). These protocols can be costly, time-consuming or provide limited assessment of neurological function. They may require extensive evaluator preparation, discouraging their use by untrained investigators. Here, we describe and validate a rapid and inexpensive, yet comprehensive, neurological exam, the Simple Neuroassessment of Asymmetric Impairment (SNAP), to assess magnitude of injury and functional recovery after unilateral TBI.
Section snippets
Animals
SNAP initially was used to test apolipoprotein E (APOE) genotype effects following TBI. C57BL/6 (WT) mice were obtained from Taconic Farms Inc. (Germantown, NY). APOE targeted replacement mice (human APOE sequences under the control of the endogenous mouse apoE promoter, C57BL/6J background) were developed by Dr. Patrick M. Sullivan (Sullivan et al., 1997) and apoE null mice (C57BL/6 background) were a generous gift from Dr. Mary Jo LaDu (Northwestern University, Evanston, IL). The genotypes of
Pooling of genotypes
SNAP initially was developed to test APOE genotype effects following TBI in mice. Behavioral outcomes were similar across the genotypes (Supplemental Fig. 1). Thus, mice of all genotypes were pooled into sham or injured groups for the purpose of validating the SNAP battery as an assessment tool for experimental TBI in mice.
Validation of the injury model
To ensure that this mouse model of moderate TBI induced detectable neurological deficits with negligible mortality, the mice were evaluated using currently accepted
Discussion
Several protocols have been established to evaluate mouse neurological status. One such protocol, the Irwin Observational Test Battery, systematically assessed 50 categories of observations (e.g., pupil size, gait, skin color, body temperature and tail pinch). It was developed to evaluate pharmacological responses in mice (Crawley, 2000). Another group designed an exhaustive series of behavioral, neurophysiological, histopathological, and imaging analyses (“SHIRPA”, Rogers et al., 1997).
Acknowledgments
We wish to thank Dr. Mary Jo LaDu for providing mice; Kristina Bielewicz and Dr. Aixiang Xue for their valuable technical assistance, as well as our chairman, Dr. Raj K. Narayan (University of Cincinnati, Department of Neurosurgery), for his continued support and encouragement. This work was funded in part by NINDS R01 NS38654 (K.I.S), and R01 AG20249 (K.A.C).
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