title: Animal models of periventricular leukomalacia.
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.
authors.affiliation: College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ehn-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.forename: Dongsun
authors.initials: D
authors.lastname: Park
authors.forename: Tae Kyun
authors.initials: TK
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Dae-Kwon
authors.initials: DK
authors.lastname: Bae
authors.forename: Goeun
authors.initials: G
authors.lastname: Yang
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Yang
authors.forename: Jangbeen
authors.initials: J
authors.lastname: Kyung
authors.forename: Dajeong
authors.initials: D
authors.lastname: Kim
authors.forename: Woo Ryoung
authors.initials: WR
authors.lastname: Lee
authors.forename: Jun-Gyo
authors.initials: JG
authors.lastname: Suh
authors.forename: Eun-Suk
authors.initials: ES
authors.lastname: Jeong
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim