Neurological Exam in Rats Following Stroke and Traumatic Brain Injury

  • Hale Z. Toklu
  • Zhiui Yang
  • Mehmet Ersahin
  • Kevin K. W. Wang
Part of the Methods in Molecular Biology book series (MIMB, volume 2011)


Using the appropriate model for testing neurological symptoms in rats is essential for the assessment of functional outcome. A number of tests have been developed to quantify the severity of neurological deficits. These tests should meet criteria such as validity, specificity, sensitivity, and utility. Although analysis of motor function shows homology in primates and rodents, the total neurological exam scores may not always reflect the clinical outcome. Therefore, the selection of the appropriate tests has critical importance when evaluating therapeutic strategies. This chapter describes Toklu’s modified neurological exam score method which can be used practically to assess neurological symptoms following traumatic brain injury (TBI) and stroke. The method is a combination of balance, muscle strength, coordination, and reflex.

Key words

Neurological exam Neurological score Rat Brain injury Stroke Trauma 



This modified scoring was first used in the Ph.D. thesis of Hale Toklu with her advisor Prof. Meral Keyer-Uysal. The authors also would like to thank Professors Goksel Sener, Berrak Yegen, Gul Ayanoglu Dulger, Tayfun Hakan, and Nihal Tumer for their supervision/contribution in brain injury studies with TBI models.

The authors are grateful to Prof. Christopher Vallandingham for language editing and proofreading.


  1. 1.
    Tupper DE, Wallace RB (1980) Utility of the neurological examination in rats. Acta Neurobiol Exp (Wars) 40:999–1003Google Scholar
  2. 2.
    Cenci MA, Whishaw IQ, Schallert T (2002) Animal models of neurological deficits: how relevant is the rat? Nat Rev Neurosci 3:574–579CrossRefGoogle Scholar
  3. 3.
    Jeon H, Ai J, Sabri M, Tariq A, Shang X, Chen G, Macdonald RL (2009) Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage. BMC Neurosci 10:103CrossRefGoogle Scholar
  4. 4.
    Zarruk JG, Garcia-Yebenes I, Romera VG, Ballesteros I, Moraga A, Cuartero MI, Hurtado O, Sobrado M, Pradillo JM, Fernandez-Lopez D, Serena J, Castillo-Melendez M, Moro MA, Lizasoain I (2011) Neurological tests for functional outcome assessment in rodent models of ischaemic stroke. Rev Neurol 53:607–618PubMedGoogle Scholar
  5. 5.
    Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H (1986) Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 17:472–476CrossRefGoogle Scholar
  6. 6.
    Garcia JH, Wagner S, Liu KF, Hu XJ (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 26:627–634; discussion 635CrossRefGoogle Scholar
  7. 7.
    Toklu HZ, Uysal MK, Kabasakal L, Sirvanci S, Ercan F, Kaya M (2009) The effects of riluzole on neurological, brain biochemical, and histological changes in early and late term of sepsis in rats. J Surg Res 152:238–248CrossRefGoogle Scholar
  8. 8.
    Biber N, Toklu HZ, Solakoglu S, Gultomruk M, Hakan T, Berkman Z, Dulger FG (2009) Cysteinyl-leukotriene receptor antagonist montelukast decreases blood-brain barrier permeability but does not prevent oedema formation in traumatic brain injury. Brain Inj 23:577–584CrossRefGoogle Scholar
  9. 9.
    Ersahin M, Toklu HZ, Cetinel S, Yuksel M, Erzik C, Berkman MZ, Yegen BC, Sener G (2010) Alpha lipoic acid alleviates oxidative stress and preserves blood brain permeability in rats with subarachnoid hemorrhage. Neurochem Res 35:418–428CrossRefGoogle Scholar
  10. 10.
    Ersahin M, Toklu HZ, Cetinel S, Yuksel M, Yegen BC, Sener G (2009) Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms. J Pineal Res 46:324–332CrossRefGoogle Scholar
  11. 11.
    Toklu HZ, Hakan T, Biber N, Solakoglu S, Ogunc AV, Sener G (2009) The protective effect of alpha lipoic acid against traumatic brain injury in rats. Free Radic Res 43:658–667CrossRefGoogle Scholar
  12. 12.
    Toklu HZ, Yang Z, Oktay S, Sakarya Y, Kirichenko N, Matheny MK, Muller-Delp J, Strang K, Scarpace PJ, Wang KKW, Tumer N (2018) Overpressure blast injury-induced oxidative stress and neuroinflammation response in rat frontal cortex and cerebellum. Behav Brain Res 340:14–22CrossRefGoogle Scholar
  13. 13.
    Fluri F, Schuhmann MK, Kleinschnitz C (2015) Animal models of ischemic stroke and their application in clinical research. Drug Des Devel Ther 9:3445–3454PubMedPubMedCentralGoogle Scholar
  14. 14.
    Megyesi JF, Vollrath B, Cook DA, Findlay JM (2000) In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:448–460; discussion 460–461CrossRefGoogle Scholar
  15. 15.
    Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14:128–142CrossRefGoogle Scholar
  16. 16.
    Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K (1994) A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80:291–300CrossRefGoogle Scholar
  17. 17.
    Ucar T, Tanriover G, Gurer I, Onal MZ, Kazan S (2006) Modified experimental mild traumatic brain injury model. J Trauma 60:558–565CrossRefGoogle Scholar
  18. 18.
    Toklu HZ, Muller-Delp J, Yang Z, Oktay S, Sakarya Y, Strang K, Ghosh P, Delp MD, Scarpace PJ, Wang KK, Tumer N (2015) The functional and structural changes in the basilar artery due to overpressure blast injury. J Cereb Blood Flow Metab 35:1950–1956CrossRefGoogle Scholar
  19. 19.
    Toklu HZ, Sakarya Y, Tumer N (2017) A proteomic evaluation of sympathetic activity biomarkers of the hypothalamus-pituitary-adrenal axis by western blotting technique following experimental traumatic brain injury. Methods Mol Biol 1598:313–325CrossRefGoogle Scholar
  20. 20.
    Cavanagh SJ, Gordon VL (2002) Grading scales used in the management of aneurysmal subarachnoid hemorrhage: a critical review. J Neurosci Nurs 34:288–295CrossRefGoogle Scholar
  21. 21.
    Wang A, Heros RC (2015) Perspective on “Modified WFNS subarachnoid hemorrhage grading system”. World Neurosurg 83:734–736CrossRefGoogle Scholar
  22. 22.
    Toklu HZ, Tumer N (2015) Oxidative stress, brain edema, blood-brain barrier permeability, and autonomic dysfunction from traumatic brain injury. In: Kobeissy FH (ed) Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects. CRC Press/Taylor & Francis, Boca Raton, FLGoogle Scholar
  23. 23.
    Kobeissy F, Mondello S, Tumer N, Toklu HZ, Whidden MA, Kirichenko N, Zhang Z, Prima V, Yassin W, Anagli J, Chandra N, Svetlov S, Wang KK (2013) Assessing neuro-systemic & behavioral components in the pathophysiology of blast-related brain injury. Front Neurol 4:186CrossRefGoogle Scholar
  24. 24.
    Ersahin M, Toklu HZ, Erzik C, Cetinel S, Akakin D, Velioglu-Ogunc A, Tetik S, Ozdemir ZN, Sener G, Yegen BC (2010) The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats. J Neurotrauma 27:1143–1155CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hale Z. Toklu
    • 1
    • 2
  • Zhiui Yang
    • 3
  • Mehmet Ersahin
    • 4
  • Kevin K. W. Wang
    • 3
  1. 1.University of Central Florida College of MedicineDepartment of Clinical SciencesGainesvilleUSA
  2. 2.HCA North Florida DivisionGraduate Medical EducationTallahasseeUSA
  3. 3.University of FloridaDepartment of Emergency MedicineGainesvilleUSA
  4. 4.Istanbul Medeniyet UniversityDepartment of NeurosurgeryIstanbulTurkey

Personalised recommendations