The optimal choices of animal models of white matter injury

Abstract

White matter injury, the most common neurological injury in preterm infants, is a major cause of chronic neurological morbidity, including cerebral palsy. Although there has been great progress in the study of the mechanism of white matter injury in newborn infants, its pathogenesis is not entirely clear, and further treatment approaches are required. Animal models are the basis of study in pathogenesis, treatment, and prognosis of white matter injury in preterm infants. Various species have been used to establish white matter injury models, including rodents, rabbits, sheep, and non-human primates. Small animal models allow cost-effective investigation of molecular and cellular mechanisms, while large animal models are particularly attractive for pathophysiological and clinical-translational studies. This review focuses on the features of commonly used white matter injury animal models, including their modelling methods, advantages, and limitations, and addresses some clinically relevant animal models that allow reproduction of the insults associated with clinical conditions that contribute to white matter injury in human infants.

Cognitive performance during adulthood in a rat model of neonatal diffuse white matter injury

“…As the incidence of preterm birth is still ominously high and the consequences of prematurity lead to serious life-long neurodevelopmental impairments, in recent years much effort has been made to develop relevant animal models that mimic non-cystic diffuse WMI, the most commonly observed form of brain injury in (extreme) preterm infants. Whereas most models apply only a single inflammatory or a single hypoxic insult to induce WMI, multiple-hit models are now acknowledged to mimic the complex etiology and pathophysiology of dWMI most closely (Silbereis et al 2010 ; for review see Zeng et al 2018 ; Kaindl et al 2009 ; Van Steenwinckel et al 2014 ; Vaes et al 2020 ). Besides representing the anatomical deficits in the target patient (i.e.…”

Postnatal Nutrition to Improve Brain Development in the Preterm Infant: A Systematic Review From Bench to Bedside

“…In addition to timing, also inclusion of an inflammatory component is thought to be key to the development of translational animal models of EoP. In recent years, rodent models of EoP have been developed (Zeng et al, 2018), including several multiple hit models that combined fetal inflammation with post-natal hypoxia (van Tilborg et al, 2018a) or multiple post-natal injections of cytokines (Rangon et al, 2018). Also larger animal models of EoP have been developed, mostly using preterm lambs (Li et al, 2016; Wassink et al, 2017; Gussenhoven et al, 2018), piglets (Andersen et al, 2016; Buddington et al, 2018), and baboons (Griffith et al, 2012).…”

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

“…To establish a neonatal rat model that could mimic WMI in human premature infants, first, in the WMI group, P3 rats were placed under anesthesia using inhaled isoflurane. The right common carotid arteries of P3 rats were isolated, ligated, and interrupted using a scalpel (keeping the interrupted condition to the end of this experiment), followed by exposure to a hypoxic environment (6% O 2 + 94% N 2 ) for 2 h. [28][29][30] In the Sham group, the right common carotid arteries of the rats were isolated without ligation, interruption, or exposure to a hypoxic environment. After the WMI model was established for 24 h, rats were administered PTN (20,40,80 μg/kg, R&D Systems) for 5 min through the lateral ventricle to establish the WMI + PTN group, and rats in the WMI + PBS group were injected with the same quantity of PBS.…”