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Development and Characterization of a Macaque Model of Focal Internal Capsular Infarcts
1Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Umezono, Tsukuba, Ibaraki, Japan.
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.
Insights
Researchers developed a new primate model for stroke by inducing infarcts in the posterior internal capsule. This model mimics human white matter stroke, showing lasting motor deficits and aiding therapeutic development.
Area of Science:
- Neuroscience
- Primate models
- Stroke research
Background:
- Macaque models with primary motor cortex (M1) lesions are common for studying motor recovery.
- Human stroke outcomes depend on white matter damage, particularly in the posterior internal capsule.
- A gap exists between macaque M1 lesion models and human white matter stroke relevant to clinical interventions.
Purpose of the Study:
- To establish a macaque model of focal white matter infarcts in the posterior internal capsule.
- To investigate the relationship between infarct volume, motor impairment, and neuronal changes.
- To provide a relevant primate model for testing stroke therapies targeting white matter damage.
Main Methods:
- Induction of focal infarcts in the posterior internal capsule of macaque monkeys using endothelin-1 (ET-1) injection.
- Monitoring infarct expansion and volume over time.
- Assessing precision grip performance and gross motor function.
- Quantifying large neuron abundance in M1.
Main Results:
- ET-1 injection successfully created expanding infarcts in the posterior internal capsule.
- Infarct volume correlated negatively with precision grip performance in the early stage.
- Dexterous hand movement impairments persisted for 3 months despite infarct volume reduction.
- Reduced large neuron abundance in M1 was associated with later-stage motor deficits.
Conclusions:
- The ET-1 induced posterior internal capsule infarct model in macaques effectively mimics human white matter stroke.
- This model demonstrates persistent motor deficits relevant to human stroke recovery.
- The model is valuable for studying neurological changes and evaluating therapeutic interventions for white matter stroke.
