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  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2021; 30(5): 356-364

Published online October 31, 2021

https://doi.org/10.5607/en21026

© The Korean Society for Brain and Neural Sciences

Precision Capsular Infarct Modeling to Produce Hand Motor Deficits in Cynomolgus Macaques

Hyung-Sun Kim1, Jeong Ho Hwang1, Su-Cheol Han1, Goo-Hwa Kang1, Ji-Young Park2 and Hyoung-Ihl Kim2,3*

1Animal Model Research Group, Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeongup 53212, 2Neuromodulation Lab, Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, 3Department of Neurosurgery, Presbyterian Medical Center, Jeonju 54987, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-62-715-3234, FAX: 82-62-715-5309
e-mail: hyoungihl@gist.ac.kr

Received: August 10, 2021; Revised: September 2, 2021; Accepted: September 30, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from gray-matter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.

Graphical Abstract


Keywords: Stroke, Internal capsule, Cynomolgus macaque, White matter