Animal Models of Cerebral Palsy: Hypoxic Brain Injury in the Newborn
Iranian Journal of Child Neurology,
Vol. 9 No. 2 (2015),
1 April 2015
,
Page 9-16
https://doi.org/10.22037/ijcn.v9i2.6389
Abstract
How to Cite This Article: Wilson MD. Animal Models of Cerebral Palsy: Hypoxic Brain Injury in the Newborn. Iran J Child Neurol. Spring
2015; 9(2):9-16.
Abstract
Objective
Hypoxic insults are implicated in the spectrum of fetal disorders, including cerebral palsy (CP). In view of the major contribution of intrapartum risk factors and prematurity to subsequent neurological morbidity and mortality in humans, this study aimed to clarify the pathophysiology of brain injury, especially periventricular white matter damage (WMD), that occur in utero to the immature and near-term fetal CNS.
Materials & Methods
An evaluation of the resulting neurological and behavioural phenotype in the newborn was performed by utilising a battery of neurobehavioural tests, including the Morris water-maze and the open-field test, followed by cerebral MRI and histopathology.
Results
This study used a murine model to examine the deleterious effects of WMD brought about by cerebral hypoxia-ischemia (HI) and the characteristic features of CP in mice. Murine models have proven themselves valuable in the area of experimental neuroscience.
Conclusion
Hypoxia-treated mice were observed to demonstrate a significant neurofunctional deficit compared with sham mice on two behavioral measures. Indeed, different brain regions, including the sensorimotor cortex, the striatum, and the hippocampus were noticeably damaged after HI insult, as determined by both MRI and histopathology. These results, albeit qualitative in nature, appear to support the pre-existing finding that the long-term neurofunctional outcome in animal subjects with CP is strongly associated with the anatomical extent and pattern of cerebral damage as determined by both delayed neuroimaging and histopathology.
- Neurodevelopmental disorder
- Prenatal hypoxia
- Cerebral palsy
- Murine model
How to Cite
References
Ikeda T, Mishima K, Yoshikawa T, Iwasaki K, Fujiwara M, Xia YX, Ikenoue T. Selective and longterm learning impairment following neonatal hypoxicischemic brain insult in rats. Behav Brain Res 2001; 118: 17-25.
Keogh JM, Badawi N. The origins of cerebral palsy. Curr Opin Neurol 2006;19: 129-134.
Sheldon RA, Sedik C, Ferriero DM. Strain-related brain injury in neonatal mice subjected to hypoxiaischemia. Brain Res 1998; 810: 114-122.
Muramatsu K, Fukuda A, Togari H, Wada Y, Nishino H. Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier. Stroke 1997; 28: 2281-2288.
Northington FJ. Brief update on animal models of hypoxic-ischemic encephalopathy and neonatal stroke. Inst Lab Anim Res J 2006; 47: 32-38.
Xue R, Sawada M, Goto S, Hurn PD, Traystman RJ, van Zijl PCM, Mori S. Rapid three-dimensional diffusion MRI facilitates the study of acute stroke in mice. Magn Reson Med 2001; 46: 183-188.
MacLennan AH. The origins of cerebral palsy – a consensus statement. MJA 1995; 162: 85-90.
Gomez R, Romero R, Ghezzi F, Yoon BH, Maxor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998; 179: 194-202.
Hagberg H, Malard C. Effect of inflammation on central nervous system development and vulnerability. Curr Opin Neurol 2005;18:117-123.
Mallard C, Welin A, Peebles D, Hagberg H, Kjellmer. White Matter Injury Following Systemic Animal Models of Cerebral Palsy: Hypoxic Brain Injury in the Newborn Endotoxemia or Asphyxia in the Fetal Sheep. Neurochemical Research 2003;28 (2): 215-223.
Rumpel H, Nedelcu J, Aguzzi A, Martin E. Late glial swelling after acute cerebral hypoxia-ischemia in the neonatal rat: a combined magnetic resonance and histochemical study. Pediatr Res 1997;42: 54-59.
Folkerth RD. Neuropathologic substrate of cerebral palsy. J Child Neurol, 2005; 20: 940-949.
Fern R, Moller T. Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci 2000;20:34-42.
Baumann N, Pham-Dinh D. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 2001;81: 871-927.
Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci, 2001;21:1302-1312.
Stigger F, Felizzola AL, Kronbauer GA, et al. Effects of fetal exposure to lipopolysaccharide, perinatal anoxia and sensorimotor restriction on motor skills and musculoskeletal tissue: Implications for an animal model of cerebral palsy. Exp Neurol 2011; 228(2):183-191.
Derrick M, Luo NL, Bregman JC, Jilling T, Ji X, Fisher K, Gladson C, Beardsley DJ, Murdoch G, Back S, Tan S. Preterm fetal hypoxia-ischemia causes hypertonia and motor deficits in the neonatal rabbit: A model for human cerebral palsy? J Neurosci 2004;24: 24-34.
Back SA, Riddle A, Hohimer R. Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury. J Child Neurol 2006; 26: 582-589.
Bell MJ, Hallenbeck JM, Gallo V. Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats. Pediatr Res 2004; 56: 541-546.
Dammann O, Kuban KC, Leviton A. Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm. Ment Retard Dev Disabil Res Rev 2002;8: 46-50.
Derrick M, Drobyshevsky A, Ji X, Tan S. A model of cerebral palsy from fetal hypoxia-ischemia. Stroke 2007; 38: 731-735.
Aden U, Dahlberg V, Fredholm BB, Lai LJ, Chen Z, Bjelke B. MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice. Stroke 2002; 33: 1405-1410.
Edgar JM, McLaughlin M, Yool D, Zhang SC, Fowler JH, Montague P, et al. Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia. J Cell Biol 2004; 166: 121-131.
Ten VS, Bradley-Moore M, Gingrich JA, Stark RI, Pinsky DJ. Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy. Behav Brain Res 2003;145: 209-219.
Volpe JJ, Kinney HC, Jensen FE, et al. The developing oligodendrocyte: key cellular target in brain injury in the premature infant. Int J Dev Neurosci 2011; 29(4):423-440.
Zhu AH, Hu YR, Liu W, Gao F, Li J, X, Zhao LH, Chen G. Systemic Evaluation of Hypoxic-Ischemic Brain Injury in Neonatal Rats. Cell biochemistry and biophysics 2014; 1-7.
van de Looij Y, Vasung L, Sizonenko SV, Hüppi PS. MRI of animal models of developmental disorders and translation to human imaging. Current opinion in neurology 2014;27(2), 157-167.
- Abstract Viewed: 624 times