title: Development and Characterization of a Macaque Model of Focal Internal Capsular Infarcts.
abstract: Several studies have used macaque monkeys with lesions induced in the primary motor cortex (M1) to investigate the recovery of motor function after brain damage. However, in human stroke patients, the severity and outcome of motor impairments depend on the degree of damage to the white matter, especially that in the posterior internal capsule, which carries corticospinal tracts. To bridge the gap between results obtained in M1-lesioned macaques and the development of clinical intervention strategies, we established a method of inducing focal infarcts at the posterior internal capsule of macaque monkeys by injecting endothelin-1 (ET-1), a vasoconstrictor peptide. The infarcts expanded between 3 days and 1 week after ET-1 injection. The infarct volume in each macaque was negatively correlated with precision grip performance 3 days and 1 week after injection, suggesting that the degree of infarct expansion may have been a cause of the impairment in hand movements during the early stage. Although the infarct volume decreased and gross movement improved, impairment of dexterous hand movements remained until the end of the behavioral and imaging experiments at 3 months after ET-1 injection. A decrease in the abundance of large neurons in M1, from which the descending motor tracts originate, was associated with this later-stage impairment. The present model is useful not only for studying neurological changes underlying deficits and recovery but also for testing therapeutic interventions after white matter infarcts in primates.
authors.affiliation: Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Umezono, Tsukuba, Ibaraki, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Umezono, Tsukuba, Ibaraki, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Higo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000008:administration & dosage; D005260:Female; D008251:Macaca; D008297:Male; D020521:Stroke / Q000473:pathology*
chemical_list: D019332:Endothelin-1