Abstract
Hypoxic-ischemic encephalopathy (HIE) is a detrimental event leading to unfavorable neurological outcomes in the newborn, the clinical phenotype of which is typically referred to as cerebral palsy. The high incidence of HIE results in a need for animal models that can replicate this human experience in order to determine the pathophysiology of injury and develop therapeutic interventions. One of the first models to be developed was, the now commonly referred to as the Rice–Vannucci model, after the student and principle investigator who first developed and described the model. Now, perhaps the best characterized and certainly the most commonly utilized model to reflect perinatal hypoxic-ischemic injury, the “Rice–Vannucci” model is the cornerstone to investigating neonatal brain injury and hypoxic-ischemic encephalopathy. This chapter describes the methodology for utilizing this model, attempt to recognize aspects of the model which have since evolved since its inception, and identify areas of caution when undertaking its use for hypoxic-ischemic encephalopathy.
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References
Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O’Sullivan F, Burton PR et al (1998) Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 317(7172):1554–1558
Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O’Sullivan F, Burton PR et al (1998) Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ 317(7172):1549–1553
Glass HC, Ferriero DM (2007) Treatment of hypoxic-ischemic encephalopathy in newborns. Curr Treat Options Neurol 9(6):414–423
Vannucci RC, Vannucci SJ (2005) Perinatal hypoxic-ischemic brain damage: evolution of an animal model. Dev Neurosci 27(2–4):81–86
Towfighi J, Zec N, Yager J, Housman C, Vannucci RC (1995) Temporal evolution of neuropathologic changes in an immature rat model of cerebral hypoxia: a light microscopic study. Acta Neuropathol 90(4):375–386
Thoresen M, Satas S, Loberg EM, Whitelaw A, Acolet D, Lindgren C et al (2001) Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. Pediatr Res 50(3):405–411
Thoresen M (1999) Cooling the asphyxiated brain - ready for clinical trials? Eur J Pediatr 158(Suppl 1):S5–S8
Thoresen M, Satas S, Puka-Sundvall M, Whitelaw A, Hallstrom A, Loberg EM et al (1997) Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins. Neuroreport 8(15):3359–3362
Srinivasakumar P, Zempel J, Wallendorf M, Lawrence R, Inder T, Mathur A (2013) Therapeutic hypothermia in neonatal hypoxic ischemic encephalopathy: electrographic seizures and magnetic resonance imaging evidence of injury. J Pediatr 163(2):465–470
Roka A, Azzopardi D (2010) Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy. Early Hum Dev 86(6):361–367
Bona E, Hagberg H, Loberg EM, Bagenholm R, Thoresen M (1998) Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short- and long-term outcome. Pediatr Res 43(6):738–745
Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG (2013) Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 1:CD003311
Shankaran S, Laptook A, Wright LL, Ehrenkranz RA, Donovan EF, Fanaroff AA et al (2002) Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics 110(2 Pt 1):377–385
Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF et al (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353(15):1574–1584
Northington FJ (2006) Brief update on animal models of hypoxic-ischemic encephalopathy and neonatal stroke. ILAR J 47(1):32–38
Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ (2013) Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol 106–107:1–16
Hagberg H, Ichord R, Palmer C, Yager JY, Vannucci SJ (2002) Animal models of developmental brain injury: relevance to human disease. A summary of the panel discussion from the Third Hershey Conference on Developmental Cerebral Blood Flow and Metabolism. Dev Neurosci 24(5):364–366
Hagberg H, Bona E, Gilland E, Puka-Sundvall M (1997) Hypoxia-ischaemia model in the 7-day-old rat: possibilities and shortcomings. Acta Paediatr Suppl 422:85–88
Levine S (1960) Anoxic-ischemic encephalopathy in rats. Am J Pathol 36:1–17
Yager JY, Wright S, Armstrong EA, Jahraus CM, Saucier DM (2006) The influence of aging on recovery following ischemic brain damage. Behav Brain Res 173(2):171–180
Yager JY, Shuaib A, Thornhill J (1996) The effect of age on susceptibility to brain damage in a model of global hemispheric hypoxia-ischemia. Brain Res Dev Brain Res 93(1–2):143–154
Rice JE 3rd, Vannucci RC, Brierley JB (1981) The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9(2):131–141
Hill CA, Fitch RH (2012) Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice. Neurol Res Int 2012:867531, Pubmed Central PMCID: 3306914
Vannucci RC, Christensen MA, Yager JY (1993) Nature, time-course, and extent of cerebral edema in perinatal hypoxic-ischemic brain damage. Pediatr Neurol 9(1):29–34
Vannucci RC, Lyons DT, Vasta F (1988) Regional cerebral blood flow during hypoxia-ischemia in immature rats. Stroke 19(2):245–250
Vannucci RC, Brucklacher RM, Vannucci SJ (2005) Glycolysis and perinatal hypoxic-ischemic brain damage. Dev Neurosci 27(2–4):185–190
Vannucci RC, Brucklacher RM, Vannucci SJ (2001) Intracellular calcium accumulation during the evolution of hypoxic-ischemic brain damage in the immature rat. Brain Res Dev Brain Res 126(1):117–120
Vannucci RC, Brucklacher RM, Vannucci SJ (1999) CSF glutamate during hypoxia-ischemia in the immature rat. Brain Res Dev Brain Res 118(1–2):147–151
Vannucci RC, Brucklacher RM (1994) Cerebral mitochondrial redox states during metabolic stress in the immature rat. Brain Res 653(1–2):141–147
Vannucci RC (1993) Mechanisms of perinatal hypoxic-ischemic brain damage. Semin Perinatol 17(5):330–337
Vannucci RC (1993) Experimental models of perinatal hypoxic-ischemic brain damage. APMIS Suppl 40:89–95
Vannucci RC (1990) Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage. Pediatr Res 27(4 Pt 1):317–326
Towfighi J, Yager JY, Housman C, Vannucci RC (1991) Neuropathology of remote hypoxic-ischemic damage in the immature rat. Acta Neuropathol 81(5):578–587
Yager J, Towfighi J, Vannucci RC (1993) Influence of mild hypothermia on hypoxic-ischemic brain damage in the immature rat. Pediatr Res 34(4):525–529
Yager JY, Asselin J (1996) Effect of mild hypothermia on cerebral energy metabolism during the evolution of hypoxic-ischemic brain damage in the immature rat. Stroke 27(5):919–925, discussion 26
Comi AM, Johnston MV, Wilson MA (2005) Immature mouse unilateral carotid ligation model of stroke. J Child Neurol 20(12):980–983
Sheldon RA, Sedik C, Ferriero DM (1998) Strain-related brain injury in neonatal mice subjected to hypoxia-ischemia. Brain Res 810(1–2):114–122
Sheldon RA, Chuai J, Ferriero DM (1996) A rat model for hypoxic-ischemic brain damage in very premature infants. Biol Neonate 69(5):327–341
Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC (2001) Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci 21(4):1302–1312
Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3(1):79–83
Yager JY (2004) Animal models of hypoxic-ischemic brain damage in the newborn. Semin Pediatr Neurol 11(1):31–46
Towfighi J, Mauger D, Vannucci RC, Vannucci SJ (1997) Influence of age on the cerebral lesions in an immature rat model of cerebral hypoxia-ischemia: a light microscopic study. Brain Res Dev Brain Res 100(2):149–160
Towfighi J, Mauger D (1998) Temporal evolution of neuronal changes in cerebral hypoxia-ischemia in developing rats: a quantitative light microscopic study. Brain Res Dev Brain Res 109(2):169–177
Hurn PD, Vannucci SJ, Hagberg H (2005) Adult or perinatal brain injury: does sex matter? Stroke 36(2):193–195
Johnston MV, Hagberg H (2007) Sex and the pathogenesis of cerebral palsy. Dev Med Child Neurol 49(1):74–78
Yager JY, Wright S, Armstrong EA, Jahraus CM, Saucier DM (2005) A new model for determining the influence of age and sex on functional recovery following hypoxic-ischemic brain damage. Dev Neurosci 27(2–4):112–120
Yager JY, Asselin J (1999) The effect of pre hypoxic-ischemic (HI) hypo and hyperthermia on brain damage in the immature rat. Brain Res Dev Brain Res 117(2):139–143
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Nguyen, A., Armstrong, E.A., Yager, J.Y. (2015). Unilateral Common Carotid Artery Ligation as a Model of Perinatal Asphyxia: The Original Rice–Vannucci Model. In: Yager, J. (eds) Animal Models of Neurodevelopmental Disorders. Neuromethods, vol 104. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2709-8_1
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DOI: https://doi.org/10.1007/978-1-4939-2709-8_1
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