Skip to main content
SpringerLink
Log in

Cognitive and Motor Function Assessments in Rodent Models of Traumatic Brain Injury

  • Protocol
  • First Online:
Pre-Clinical and Clinical Methods in Brain Trauma Research

Part of the book series: Neuromethods ((NM,volume 139))

Abstract

Cognitive and motor dysfunction is common in people who have experienced a traumatic brain injury (TBI). These deficits can include memory loss, learning impairment, dizziness, difficulty with balance, and loss of fine motor control and coordination. Cognitive function and vestibulomotor tasks have been widely used in clinically relevant rodent models of experimental TBI to study the relationship of neurobehavioral dysfunction to injury severity, secondary injury mechanisms, or putative therapeutic interventions. Here we describe paradigms for the novel object recognition task, a test of memory, and beam walking and rotarod tasks, tests of coordinated motor function. Key advantages and disadvantages are presented, and potential problems and adaptations of these behavioral tests are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Langlois JA, Rutland-Brown W, Wald MM (2006) The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21(5):375–378

    Article  PubMed  Google Scholar 

  2. Bolton Hall AN, Joseph B, Brelsfoard JM, Saatman KE (2016) Repeated closed head injury in mice results in sustained motor and memory deficits and chronic cellular changes. PLoS One 11(7):e0159442. https://doi.org/10.1371/journal.pone.0159442

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Madathil SK, Saatman KE (2015) IGF-1/IGF-R signaling in traumatic brain injury: impact on cell survival, neurogenesis, and behavioral outcome. In: Kobeissy FH (ed) Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects. Frontiers in Neuroengineering, Boca Raton, FL

    Google Scholar 

  4. Bales JW, Macfarlane K, Edward Dixon C (2012) Neurobehavioral assessments of traumatic brain injury. In: Chen J, Xu XM, Xu ZC, Zhang JH (eds) Animal models of acute neurological injuries II, vol vol II. Humana Springer Science+Business Media, LLC, New York, pp 377–384. https://doi.org/10.1007/978-1-61779-782-8_34

    Chapter  Google Scholar 

  5. Bales JW, Macfarlane K, Edward Dixon C (2012) Vestibular assessments following traumatic brain injury. In: Chen J, Xu XM, Xu ZC, Zhang JH (eds) Animal models of acute neurological injuries II, vol vol II. Humana Springer Science+Business Media, LLC, New York, pp 385–396. https://doi.org/10.1007/978-1-61779-782-8_33

    Chapter  Google Scholar 

  6. Fujimoto ST, Longhi L, Saatman KE, Conte V, Stocchetti N, McIntosh TK (2004) Motor and cognitive function evaluation following experimental traumatic brain injury. Neurosci Biobehav Rev 28(4):365–378. https://doi.org/10.1016/j.neubiorev.2004.06.002

    Article  PubMed  Google Scholar 

  7. Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31(1):47–59

    Article  PubMed  CAS  Google Scholar 

  8. Grayson B, Leger M, Piercy C, Adamson L, Harte M, Neill JC (2015) Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents. Behav Brain Res 285:176–193. https://doi.org/10.1016/j.bbr.2014.10.025

    Article  PubMed  Google Scholar 

  9. Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13(2):93–110. https://doi.org/10.1007/s10339-011-0430-z

    Article  PubMed  CAS  Google Scholar 

  10. Silvers JM, Harrod SB, Mactutus CF, Booze RM (2007) Automation of the novel object recognition task for use in adolescent rats. J Neurosci Methods 166(1):99–103. https://doi.org/10.1016/j.jneumeth.2007.06.032

    Article  PubMed  PubMed Central  Google Scholar 

  11. Goulart BK, de Lima MN, de Farias CB, Reolon GK, Almeida VR, Quevedo J, Kapczinski F, Schroder N, Roesler R (2010) Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience 167(4):969–973. https://doi.org/10.1016/j.neuroscience.2010.03.032

    Article  PubMed  CAS  Google Scholar 

  12. Rachmany L, Tweedie D, Rubovitch V, Yu QS, Li Y, Wang JY, Pick CG, Greig NH (2013) Cognitive impairments accompanying rodent mild traumatic brain injury involve p53-dependent neuronal cell death and are ameliorated by the tetrahydrobenzothiazole PFT-alpha. PLoS One 8(11):e79837. https://doi.org/10.1371/journal.pone.0079837

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Rubovitch V, Zilberstein Y, Chapman J, Schreiber S, Pick CG (2017) Restoring GM1 ganglioside expression ameliorates axonal outgrowth inhibition and cognitive impairments induced by blast traumatic brain injury. Sci Rep 7:41269. https://doi.org/10.1038/srep41269

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Muradashvili N, Benton RL, Saatman KE, Tyagi SC, Lominadze D (2015) Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice. Metab Brain Dis 30(2):411–426. https://doi.org/10.1007/s11011-014-9550-3

    Article  PubMed  CAS  Google Scholar 

  15. Ouyang W, Yan Q, Zhang Y, Fan Z (2017) Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood. PLoS One 12(2):e0171976. https://doi.org/10.1371/journal.pone.0171976

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Madathil SK, Carlson SW, Brelsfoard JM, Ye P, D’Ercole AJ, Saatman KE (2013) Astrocyte-specific overexpression of insulin-like growth Factor-1 protects hippocampal neurons and reduces behavioral deficits following traumatic brain injury in mice. PLoS One 8(6):e67204. https://doi.org/10.1371/journal.pone.0067204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Haus DL, Lopez-Velazquez L, Gold EM, Cunningham KM, Perez H, Anderson AJ, Cummings BJ (2016) Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury. Exp Neurol 281:1–16. https://doi.org/10.1016/j.expneurol.2016.04.008

    Article  PubMed  CAS  Google Scholar 

  18. Tsenter J, Beni-Adani L, Assaf Y, Alexandrovich AG, Trembovler V, Shohami E (2008) Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions. J Neurotrauma 25(4):324–333. https://doi.org/10.1089/neu.2007.0452

    Article  PubMed  Google Scholar 

  19. Schoch KM, Evans HN, Brelsfoard JM, Madathil SK, Takano J, Saido TC, Saatman KE (2012) Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury. Exp Neurol 236(2):371–382. https://doi.org/10.1016/j.expneurol.2012.04.022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Cohen SJ, Stackman RW Jr (2015) Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res 285:105–117. https://doi.org/10.1016/j.bbr.2014.08.002

    Article  PubMed  Google Scholar 

  21. Cai L, Gibbs RB, Johnson DA (2012) Recognition of novel objects and their location in rats with selective cholinergic lesion of the medial septum. Neurosci Lett 506(2):261–265. https://doi.org/10.1016/j.neulet.2011.11.019

    Article  PubMed  CAS  Google Scholar 

  22. Prins ML, Hales A, Reger M, Giza CC, Hovda DA (2010) Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments. Dev Neurosci 32(5-6):510–518. https://doi.org/10.1159/000316800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Perez-Garcia G, Guzman-Quevedo O, Da Silva Aragao R, Bolanos-Jimenez F (2016) Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis. Sci Rep 6:21275. https://doi.org/10.1038/srep21275

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Lee YA, Kim YJ, Goto Y (2016) Cognitive and affective alterations by prenatal and postnatal stress interaction. Physiol Behav 165:146–153. https://doi.org/10.1016/j.physbeh.2016.07.014

    Article  PubMed  CAS  Google Scholar 

  25. Gao Y, Li J, Wu L, Zhou C, Wang Q, Li X, Zhou M, Wang H (2016) Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: autophagy and the PI3K/AKT pathways as a potential mechanism. J Surg Res 206(1):67–76. https://doi.org/10.1016/j.jss.2016.07.014

    Article  PubMed  CAS  Google Scholar 

  26. Yu YW, Hsieh TH, Chen KY, Wu JC, Hoffer BJ, Greig NH, Li Y, Lai JH, Chang CF, Lin JW, Chen YH, Yang LY, Chiang YH (2016) Glucose-dependent insulinotropic polypeptide ameliorates mild traumatic brain injury-induced cognitive and sensorimotor deficits and neuroinflammation in rats. J Neurotrauma 33(22):2044–2054. https://doi.org/10.1089/neu.2015.4229

    Article  PubMed  PubMed Central  Google Scholar 

  27. Simon-O’Brien E, Gauthier D, Riban V, Verleye M (2016) Etifoxine improves sensorimotor deficits and reduces glial activation, neuronal degeneration, and neuroinflammation in a rat model of traumatic brain injury. J Neuroinflammation 13(1):203. https://doi.org/10.1186/s12974-016-0687-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Pleasant JM, Carlson SW, Mao H, Scheff SW, Yang KH, Saatman KE (2011) Rate of neurodegeneration in the mouse controlled cortical impact model is influenced by impactor tip shape: implications for mechanistic and therapeutic studies. J Neurotrauma 28(11):2245–2262. https://doi.org/10.1089/neu.2010.1499

    Article  PubMed  PubMed Central  Google Scholar 

  29. Stanley JL, Lincoln RJ, Brown TA, McDonald LM, Dawson GR, Reynolds DS (2005) The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines. J Psychopharmacol 19(3):221–227. https://doi.org/10.1177/0269881105051524

    Article  PubMed  CAS  Google Scholar 

  30. Hamm RJ, Pike BR, O’Dell DM, Lyeth BG, Jenkins LW (1994) The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma 11(2):187–196. https://doi.org/10.1089/neu.1994.11.187

    Article  PubMed  CAS  Google Scholar 

  31. Luong TN, Carlisle HJ, Southwell A, Patterson PH (2011) Assessment of motor balance and coordination in mice using the balance beam. J Vis Exp 49. https://doi.org/10.3791/2376

  32. Statler KD, Alexander H, Vagni V, Holubkov R, Dixon CE, Clark RS, Jenkins L, Kochanek PM (2006) Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury. Brain Res 1076(1):216–224. https://doi.org/10.1016/j.brainres.2005.12.106

    Article  PubMed  CAS  Google Scholar 

  33. Desai A, Park T, Barnes J, Kevala K, Chen H, Kim HY (2016) Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by alpha-linolenic acid supplementation in mice. J Neuroinflammation 13(1):253. https://doi.org/10.1186/s12974-016-0714-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Dunham NW, Miya TS (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc 46(3):208–209

    Article  PubMed  CAS  Google Scholar 

  35. Monville C, Torres EM, Dunnett SB (2006) Comparison of incremental and accelerating protocols of the rotarod test for the assessment of motor deficits in the 6-OHDA model. J Neurosci Methods 158(2):219–223. https://doi.org/10.1016/j.jneumeth.2006.06.001

    Article  PubMed  Google Scholar 

  36. Rozas G, Guerra MJ, Labandeira-Garcia JL (1997) An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. Brain Res Brain Res Protoc 2(1):75–84

    Article  PubMed  CAS  Google Scholar 

  37. Im SH, Yu JH, Park ES, Lee JE, Kim HO, Park KI, Kim GW, Park CI, Cho SR (2010) Induction of striatal neurogenesis enhances functional recovery in an adult animal model of neonatal hypoxic-ischemic brain injury. Neuroscience 169(1):259–268. https://doi.org/10.1016/j.neuroscience.2010.04.038

    Article  CAS  PubMed  Google Scholar 

  38. Yu W, Parakramaweera R, Teng S, Gowda M, Sharad Y, Thakker-Varia S, Alder J, Sesti F (2016) Oxidation of KCNB1 potassium channels causes neurotoxicity and cognitive impairment in a mouse model of traumatic brain injury. J Neurosci 36(43):11084–11096. https://doi.org/10.1523/JNEUROSCI.2273-16.2016

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Mannix R, Berglass J, Berkner J, Moleus P, Qiu J, Andrews N, Gunner G, Berglass L, Jantzie LL, Robinson S, Meehan WP 3rd (2014) Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury. J Neurosurg 121(6):1342–1350. https://doi.org/10.3171/2014.7.JNS14272

    Article  PubMed  PubMed Central  Google Scholar 

  40. Byard RW, Donkin J, Vink R (2017) The forensic implications of amphetamine intoxication in cases of inflicted blunt craniocerebral trauma. J Forensic Sci 63:151–153. https://doi.org/10.1111/1556-4029.13509

    Article  PubMed  CAS  Google Scholar 

  41. Dachir S, Shabashov D, Trembovler V, Alexandrovich AG, Benowitz LI, Shohami E (2014) Inosine improves functional recovery after experimental traumatic brain injury. Brain Res 1555:78–88. https://doi.org/10.1016/j.brainres.2014.01.044

    Article  PubMed  CAS  Google Scholar 

  42. Lagraoui M, Latoche JR, Cartwright NG, Sukumar G, Dalgard CL, Schaefer BC (2012) Controlled cortical impact and craniotomy induce strikingly similar profiles of inflammatory gene expression, but with distinct kinetics. Front Neurol 3:155. https://doi.org/10.3389/fneur.2012.00155

    Article  PubMed  PubMed Central  Google Scholar 

  43. Laurer HL, Bareyre FM, Lee VM, Trojanowski JQ, Longhi L, Hoover R, Saatman KE, Raghupathi R, Hoshino S, Grady MS, McIntosh TK (2001) Mild head injury increasing the brain’s vulnerability to a second concussive impact. J Neurosurg 95(5):859–870. https://doi.org/10.3171/jns.2001.95.5.0859

    Article  PubMed  CAS  Google Scholar 

  44. Lindner MD, Plone MA, Cain CK, Frydel B, Francis JM, Emerich DF, Sutton RL (1998) Dissociable long-term cognitive deficits after frontal versus sensorimotor cortical contusions. J Neurotrauma 15(3):199–216. https://doi.org/10.1089/neu.1998.15.199

    Article  PubMed  CAS  Google Scholar 

  45. O’Connor CA, Cernak I, Johnson F, Vink R (2007) Effects of progesterone on neurologic and morphologic outcome following diffuse traumatic brain injury in rats. Exp Neurol 205(1):145–153. https://doi.org/10.1016/j.expneurol.2007.01.034

    Article  PubMed  CAS  Google Scholar 

  46. Yang SH, Gustafson J, Gangidine M, Stepien D, Schuster R, Pritts TA, Goodman MD, Remick DG, Lentsch AB (2013) A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits. J Surg Res 184(2):981–988. https://doi.org/10.1016/j.jss.2013.03.075

    Article  PubMed  PubMed Central  Google Scholar 

  47. Shiotsuki H, Yoshimi K, Shimo Y, Funayama M, Takamatsu Y, Ikeda K, Takahashi R, Kitazawa S, Hattori N (2010) A rotarod test for evaluation of motor skill learning. J Neurosci Methods 189(2):180–185. https://doi.org/10.1016/j.jneumeth.2010.03.026

    Article  PubMed  Google Scholar 

  48. Yan EB, Johnstone VP, Alwis DS, Morganti-Kossmann MC, Rajan R (2013) Characterising effects of impact velocity on brain and behaviour in a model of diffuse traumatic axonal injury. Neuroscience 248:17–29. https://doi.org/10.1016/j.neuroscience.2013.05.045

    Article  PubMed  CAS  Google Scholar 

  49. Srodulski S, Sharma S, Bachstetter AB, Brelsfoard JM, Pascual C, Xie XS, Saatman KE, Van Eldik LJ, Despa F (2014) Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin. Mol Neurodegener 9:30. https://doi.org/10.1186/1750-1326-9-30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Rustay NR, Wahlsten D, Crabbe JC (2003) Influence of task parameters on rotarod performance and sensitivity to ethanol in mice. Behav Brain Res 141(2):237–249

    Article  PubMed  CAS  Google Scholar 

  51. Scherbel U, Raghupathi R, Nakamura M, Saatman KE, Trojanowski JQ, Neugebauer E, Marino MW, McIntosh TK (1999) Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci U S A 96(15):8721–8726

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

Supported, in part, by NIH R01 NS072302 and Kentucky Spinal Cord and Head Injury Research Trust grants 14-12A and 14-13A.

Author information

Authors and Affiliations

  1. Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY, USA

    Danielle Scott & Kathryn E. Saatman

Authors
  1. Danielle Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn E. Saatman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathryn E. Saatman .

Editor information

Editors and Affiliations

  1. Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Sciences Center at Houston, Houston, Texas, USA

    Amit K. Srivastava

  2. Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Sciences Center at Houston, Houston, Texas, USA

    Charles S. Cox

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Scott, D., Saatman, K.E. (2018). Cognitive and Motor Function Assessments in Rodent Models of Traumatic Brain Injury. In: Srivastava, A., Cox, C. (eds) Pre-Clinical and Clinical Methods in Brain Trauma Research. Neuromethods, vol 139. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8564-7_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8564-7_9

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8563-0

  • Online ISBN: 978-1-4939-8564-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation