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Weight-Drop Method for Inducing Closed Head Diffuse Traumatic Brain Injury

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Neuroprotection

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2761))

Abstract

Traumatic brain injury (TBI) is one of the foremost causes of disability and death globally. Prerequisites for successful therapy of disabilities associated with TBI involved improved knowledge of the neurobiology of TBI, measurement of quantitative changes in recovery dynamics brought about by therapy, and the translation of quantitative methodologies and techniques that were successful in tracking recovery in preclinical models to human TBI. Frequently used animal models of TBI in research and development include controlled cortical impact, fluid percussion injury, blast injury, penetrating blast brain injury, and weight-drop impact acceleration models. Preclinical models of TBI benefit from controlled injury settings and the best prospects for biometric quantification of injury and therapy-induced gradual recovery from disabilities. Impact acceleration closed head TBI paradigm causes diffuse TBI (DTBI) without substantial focal brain lesions in rats. DTBI is linked to a significant rate of death, morbidity, and long-term disability. DTBI is difficult to diagnose at the time of hospitalization with imaging techniques making it challenging to take prompt therapeutic action. The weight-drop method without craniotomy is an impact acceleration closed head DTBI model that is used to induce mild/moderate diffuse brain injuries in rodents. Additionally, we have characterized neuropathological and neurobehavioral outcomes of the weight-drop model without craniotomy for inducing closed head DTBI of graded severity with a range of mass of weights (50–450 gm). This chapter also discusses techniques and protocols for measuring numerous functional disabilities and pathological changes in the brain brought on by DTBI.

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References

  1. Dewan M, Rattani A, Gupta S et al (2018) Estimating the global incidence of traumatic brain injury. J Neurosurg 130:1–18

    Google Scholar 

  2. Coburn K (1992) Traumatic brain injury: the silent epidemic. AACN Adv Crit Care 3:9–18

    Article  CAS  Google Scholar 

  3. Narayan RK, Michel ME, Ansell B et al (2002) Clinical trials in head injury. J Neurotrauma 19:503–557

    Article  PubMed  Google Scholar 

  4. Beauchamp K, Mutlak H, Smith WR et al (2008) Pharmacology of traumatic brain injury: where is the “golden bullet”? Mol Med 14:731–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Briones TL (2015) Chapter 3 animal models of traumatic brain injury: is there an optimal model that parallels human brain injury? Annu Rev Nurs Res 33:31–73

    Article  PubMed  Google Scholar 

  6. Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14:128–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mcintosh TK, Noble L, Andrews B, Faden AI (1987) Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent Nerv Syst Trauma 4:119–134

    Article  CAS  PubMed  Google Scholar 

  8. Lighthall JW (1988) Controlled cortical impact: a new experimental brain injury model. J Neurotrauma 5:1–15

    Article  CAS  PubMed  Google Scholar 

  9. Williams AJ, Hartings JA, Lu X-CM et al (2006) Penetrating ballistic-like brain injury in the rat: differential time courses of hemorrhage, cell death, inflammation, and remote degeneration. J Neurotrauma 23:1828–1846

    Article  PubMed  Google Scholar 

  10. Cheng J, Gu J, Ma Y et al (2010) Development of a rat model for studying blast-induced traumatic brain injury. J Neurol Sci 294:23–28

    Article  PubMed  Google Scholar 

  11. Feeney DM, Boyeson MG, Linn RT et al (1981) Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res 211:67–77

    Article  CAS  PubMed  Google Scholar 

  12. DeFord SM, Wilson MS, Rice AC et al (2002) Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice. J Neurotrauma 19:427–438

    Article  PubMed  Google Scholar 

  13. Kalish BT, Whalen MJ (2016) Weight drop models in traumatic brain injury BT. In: Kobeissy FH, Dixon CE, Hayes RL, Mondello S (eds) Injury models of the central nervous system: methods and protocols. Springer, New York, pp 193–209

    Chapter  Google Scholar 

  14. Laurer HL, Lenzlinger PM, McIntosh TK (2000) Models of traumatic brain injury. Eur J Trauma 26:95–110

    Article  Google Scholar 

  15. Bales JW, Bonow RH, Ellenbogen RG (2018) Closed head injury. In: Principles of neurological surgery, pp 366–389.e4

    Chapter  Google Scholar 

  16. Rungruangsak K, Poriswanish N (2021) Pathology of fatal diffuse brain injury in severe non-penetrating head trauma. J Forensic Legal Med 82:102226

    Article  Google Scholar 

  17. Jeret JS, Mandell M, Anziska B et al (1993) Clinical predictors of abnormality disclosed by computed tomography after mild head trauma. Neurosurgery 32:9–16

    Article  CAS  PubMed  Google Scholar 

  18. Lee H, Wintermark M, Gean AD et al (2008) Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 25:1049–1056

    Article  PubMed  Google Scholar 

  19. Marshall LF, Marshall SB, Klauber MR et al (1991) A new classification of head injury based on computerized tomography. J Neurosurg 75:S14–S20

    Article  Google Scholar 

  20. Walker WC (2007) Motor impairment after severe traumatic brain injury: a longitudinal multicenter study. J Rehabil Res Dev 44:975–982

    Article  PubMed  Google Scholar 

  21. Beaumont A, Marmarou A, Czigner A et al (1999) The impact-acceleration model of head injury: injury severity predicts motor and cognitive performance after trauma. Neurol Res 21:742–754

    Article  CAS  PubMed  Google Scholar 

  22. Barot J, Saxena B (2021) Therapeutic effects of eugenol in a rat model of traumatic brain injury: a behavioral, biochemical, and histological study. J Tradit Complement Med 11:318–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Barzó P, Marmarou A, Fatouros P et al (1997) Acute blood-brain barrier changes in experimental closed head injury as measured by MRI and Gd-DTPA. In: Brain edema X. Springer Vienna, Vienna, pp 243–246

    Chapter  Google Scholar 

  24. Zusman BE, Kochanek PM, Jha RM (2020) Cerebral edema in traumatic brain injury: a historical framework for current therapy. Curr Treat Options Neurol 22:9

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ikeda Y, Long DM (1990) The molecular basis of brain injury and brain edema: the role of oxygen free radicals. Neurosurgery 27:1–11

    Article  CAS  PubMed  Google Scholar 

  26. Marmarou A, Foda MAA-E, Brink W van den et al (1994) A new model of diffuse brain injury in rats: Part I: pathophysiology and biomechanics. J Neurosurg 80:291–300

    Article  CAS  PubMed  Google Scholar 

  27. Marmarou CR, Prieto R, Taya K et al (2009) Marmarou weight drop injury model BT. In: Chen J, Xu ZC, Xu X-M, Zhang JH (eds) Animal models of acute neurological injuries. Humana Press, Totowa, pp 393–407

    Chapter  Google Scholar 

  28. Abd-Elfattah Foda MA, Marmarou A (1994) A new model of diffuse brain injury in rats: Part II: morphological characterization. J Neurosurg 80:301–313

    Article  Google Scholar 

  29. Ogawa N, Hirose Y, Ohara S et al (1985) A simple quantitative bradykinesia test in MPTP-treated mice. Res Commun Chem Pathol Pharmacol 50:435–441

    CAS  PubMed  Google Scholar 

  30. Goldstein LB, Davis JN (1990) Beam-walking in rats: studies towards developing an animal model of functional recovery after brain injury. J Neurosci Methods 31:101–107

    Article  CAS  PubMed  Google Scholar 

  31. Leconte C, Benedetto C, Lentini F et al (2020) Histological and behavioral evaluation after traumatic brain injury in mice: a ten months follow-up study. J Neurotrauma 37:1342–1357

    Article  PubMed  Google Scholar 

  32. Lad KA, Maheshwari A, Saxena B (2019) Repositioning of an anti-depressant drug, agomelatine as therapy for brain injury induced by craniotomy. Drug Discov Ther 13:189–197

    Article  CAS  PubMed  Google Scholar 

  33. Katayama S, Shionoya H, Ohtake S (1978) A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats. Microbiol Immunol 22:89–101

    Article  CAS  PubMed  Google Scholar 

  34. Shigeno T, Brock M, Shigeno S et al (1982) The determination of brain water content: microgravimetry versus drying-weighing method. J Neurosurg 57:99–107

    Article  CAS  PubMed  Google Scholar 

  35. Palmieri M, Frati A, Santoro A et al (2021) Diffuse axonal injury: clinical prognostic factors, molecular experimental models and the impact of the trauma related oxidative stress. An extensive review concerning milestones and advances. Int J Mol Sci 22:10865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. In: Methods in enzymology. Elsevier, pp 421–431

    Google Scholar 

  37. Hevel JM, Marletta MA (1994) Nitric-oxide synthase assays. In: Methods in enzymology. Elsevier, pp 250–258

    Google Scholar 

  38. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  39. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  PubMed  Google Scholar 

  40. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  41. Tucker LB, Fu AH, McCabe JT (2016) Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research. J Neurotrauma 33:880–894

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wagner AK, Kline AE, Ren D et al (2007) Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury. Behav Brain Res 181:200–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wagner AK, Willard LA, Kline AE et al (2004) Evaluation of estrous cycle stage and gender on behavioral outcome after experimental traumatic brain injury. Brain Res 998:113–121

    Article  CAS  PubMed  Google Scholar 

  44. Schifilliti D, Grasso G, Conti A, Fodale V (2010) Anaesthetic-related neuroprotection: intravenous or inhalational agents? CNS Drugs 24:893–907

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India

    Bhagawati Saxena & Bhavna Bohra

  2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Ahmedabad, Gandhinagar, Gujarat, India

    Krishna A. Lad

Authors
  1. Bhagawati Saxena
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  2. Bhavna Bohra
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  3. Krishna A. Lad
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Corresponding author

Correspondence to Bhagawati Saxena .

Editor information

Editors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA

    Swapan K. Ray

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Saxena, B., Bohra, B., Lad, K.A. (2024). Weight-Drop Method for Inducing Closed Head Diffuse Traumatic Brain Injury. In: Ray, S.K. (eds) Neuroprotection. Methods in Molecular Biology, vol 2761. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3662-6_38

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  • DOI: https://doi.org/10.1007/978-1-0716-3662-6_38

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3661-9

  • Online ISBN: 978-1-0716-3662-6

  • eBook Packages: Springer Protocols

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