Lab Anim Res.  2011 Jun;27(2):77-84. 10.5625/lar.2011.27.2.77.

Animal Models of Periventricular Leukomalacia

• Choi EK
• Park D
• Kim TK
• Lee SH
• Bae DK
• Yang G
• Yang YH
• Kyung J
• Kim D
• Lee WR
• Suh JG
• Jeong ES
• Kim SU
• Kim YB

• KMID: 2053655
• DOI: http://doi.org/10.5625/lar.2011.27.2.77

Abstract

Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics.

Keyword

Periventricular leukomalacia; white matter injury; cerebral palsy; hypoperfusion (hypoxia-ischemia); inflammation (lipopolysaccharide); premyelinating oligodendrocytes

MeSH Terms

Animals
Brain
Brain Injuries
Carotid Arteries
Central Nervous System
Cerebral Palsy
Humans
Infant, Newborn
Inflammation
Leukomalacia, Periventricular
Models, Animal
Neurotoxins
Oligodendroglia
Oxygen
Rats
Rodentia
Neurotoxins
Oxygen

Figure

• 

  Figure 1 Developmental stage-dependent periventricular leukomalacia of rodents induced by hypoxia-ischemia. PND, post-natal day; WMI, white matter injury.

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