Animal Models of Periventricular Leukomalacia.
- Author:
Ehn Kyoung CHOI
1
;
Dongsun PARK
;
Tae Kyun KIM
;
Sun Hee LEE
;
Dae Kwon BAE
;
Goeun YANG
;
Yun Hui YANG
;
Jangbeen KYUNG
;
Dajeong KIM
;
Woo Ryoung LEE
;
Jun Gyo SUH
;
Eun Suk JEONG
;
Seung U KIM
;
Yun Bae KIM
Author Information
- Publication Type:Review
- Keywords: Periventricular leukomalacia; white matter injury; cerebral palsy; hypoperfusion (hypoxia-ischemia); inflammation (lipopolysaccharide); premyelinating oligodendrocytes
- MeSH: Animals; Brain; Brain Injuries; Carotid Arteries; Central Nervous System; Cerebral Palsy; Humans; Infant, Newborn; Inflammation; Leukomalacia, Periventricular; Models, Animal; Neurotoxins; Oligodendroglia; Oxygen; Rats; Rodentia
- From:Laboratory Animal Research 2011;27(2):77-84
- CountryRepublic of Korea
- Language:English
- 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.
