Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairments and cerebral palsy

Redox Biology

Jeannette Vasquez-Vivar¹  Karthikeyan Thirugnanam¹  Kehuan Luo²  Zhongjie Shi²  Sidhartha Tan² 

[1] Department of Biophysics and Redox Biology Program, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA;Wayne State University School of Medicine and Children's Hospital of Michigan, 3901 Beaubien, Room 5177, Carls Bldg., Detroit, MI 48201, USA;

关键词: Hypertonia;    Neuronal nitric oxide synthase;    Reactive oxygen species;    Dopamine;    Fetal brain MRI;    Sepiapterin;   

DOI  :  10.1016/j.redox.2017.08.002

来源: DOAJ

【 摘 要 】

Antenatal brain hypoxia-ischemia, which occurs in cerebral palsy, is considered a significant cause of motor impairments in children. The mechanisms by which antenatal hypoxia-ischemia causes brain injury and motor deficits still need to be elucidated. Tetrahydrobiopterin is an important enzyme cofactor that is necessary to produce neurotransmitters and to maintain the redox status of the brain. A genetic deficiency of this cofactor from mutations of biosynthetic or recycling enzymes is a well-recognized factor in the development of childhood neurological disorders characterized by motor impairments, developmental delay, and encephalopathy. Experimental hypoxia-ischemia causes a decline in the availability of tetrahydrobiopterin in the immature brain. This decline coincides with the loss of brain function, suggesting this occurrence contributes to neuronal dysfunction and motor impairments. One possible mechanism linking tetrahydrobiopterin deficiency, hypoxia-ischemia, and neuronal injury is oxidative injury. Evidence of the central role of the developmental biology of tetrahydrobiopterin in response to hypoxic ischemic brain injury, especially the development of motor deficits, is discussed.

【 授权许可】

Unknown