Towards improved animal models of neonatal white matter injury associated with cerebral palsy

Abstract

Newborn neurological injuries are the leading cause of intellectual and motor disabilities that are associated with cerebral palsy. Cerebral white matter injury is a common feature in hypoxic-ischemic encephalopathy (HIE), which affects fullterm infants, and in periventricular leukomalacia (PVL), which affects preterm infants. This article discusses recent efforts to model neonatal white matter injury using mammalian systems. We emphasize that a comprehensive understanding of oligodendrocyte development and physiology is crucial for obtaining new insights into the pathobiology of HIE and PVL as well as for the generation of more sophisticated and faithful animal models.

Sexual dimorphism and brain lateralization impact behavioral and histological outcomes following hypoxia–ischemia in P3 and P7 rats

“…Q5 Special care has been given to the preterm ones, 26 since HI incidence (1-3 per 1000 live full-term births) 27 increases to 40 per 1000 in preterm children with very 28 low birth weight along the last decades (Kirby, 2012;29 Salmaso et al, 2014). 30 Human and animal evidence shows the nature of 31 lesions caused by HI is related, at least in part, to the 32 gestational age in which the insult is experienced 33 (Towfighi et al, 1997;Silbereis et al, 2010). In term chil-34 dren (between 30 and 34 weeks), selective neuronal 35 necrosis, especially in the parieto-occipital lobes and focal 36 encephalic lesions are the most common causes of 37 encephalopathy and of seizures (Silbereis et al, 2010;38 Shrivastava et al, 2012).…”

“…30 Human and animal evidence shows the nature of 31 lesions caused by HI is related, at least in part, to the 32 gestational age in which the insult is experienced 33 (Towfighi et al, 1997;Silbereis et al, 2010). In term chil-34 dren (between 30 and 34 weeks), selective neuronal 35 necrosis, especially in the parieto-occipital lobes and focal 36 encephalic lesions are the most common causes of 37 encephalopathy and of seizures (Silbereis et al, 2010;38 Shrivastava et al, 2012). On the other hand, premature 39 infants are especially prone to develop brain lesions such 40 as intraventricular hemorrhage and periventricular leuko-41 malacia (PVL) after perinatal white matter injury (Stadlin 42 et al, 2003;Silbereis et al, 2010).…”

“…In term chil-34 dren (between 30 and 34 weeks), selective neuronal 35 necrosis, especially in the parieto-occipital lobes and focal 36 encephalic lesions are the most common causes of 37 encephalopathy and of seizures (Silbereis et al, 2010;38 Shrivastava et al, 2012). On the other hand, premature 39 infants are especially prone to develop brain lesions such 40 as intraventricular hemorrhage and periventricular leuko-41 malacia (PVL) after perinatal white matter injury (Stadlin 42 et al, 2003;Silbereis et al, 2010). Such particularities 43 on neuropathological issues after hypoxic-ischemic 44 events probably reflect the differential vulnerability of spe-45 cific brain regions due to different stages of cellular 46 development.…”

Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury

“…Several forms of neonatal brain injury are associated with the development of cerebral palsy (CP) [1][2][3][4] ; these include periventricular leukomalacia (PVL), intraventricular hemorrhage, periventricular hemorrhagic infarction, neonatal stroke, hypoxic-ischemic encephalopathy, and combined gray and white matter injury ( Table 1). …”

“…No specific preventive or therapeutic strategies, however, exist for PVL. Thus, PVL has become the major brain injury in premature inNeurosci Bull April 1, 2013, 29 (2): [229][230][231][232][233][234][235][236][237][238] 230 fants leading to CP and cognitive impairments. In addition, hypoxic-ischemic encephalopathy, asphyxia and neonatal stroke can also cause CP, which is often associated with combined gray and white matter lesions [2,3] .…”