Transcortical photothrombotic pyramidotomy model with persistent motor deficits

• Published in: PloS one 2018-12, Vol.13 (12), p.e0204842-e0204842
• Main Authors: Song, Hanlim, Cho, Jongwook, Lee, Sunwoo, Park, Ji-Young, Choi, Byung-Moon, Kim, Min Sun, Kim, Weon Gyeong, Lee, Min-Cheol, Kim, Hyoung-Ihl
• Format: Article
• Language: English
• Subjects: Animals; Auditory Cortex - diagnostic imaging; Auditory Cortex - physiopathology; Biology and Life Sciences; Brain research; Cerebellum; Cortex (auditory); Cortex (somatosensory); Disease Models, Animal; Engineering; Fibers; Fluorodeoxyglucose F18 - pharmacology; Glucose; Glucose metabolism; Hemispheres; Male; Medical research; Medicine and Health Sciences; Metabolism; Mortality; Motor Cortex - diagnostic imaging; Motor Cortex - physiopathology; Motor Disorders - diagnostic imaging; Motor Disorders - physiopathology; Motor Neurons; Motors; Neuroimaging; Optical fibers; Physical Sciences; Positron-Emission Tomography; Preservation; Pyramidal tracts; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Respiration; Respiratory function; Rodents; Somatosensory cortex; Spinal cord; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0204842

Traditional pyramidotomy models have a high mortality rate from breathing difficulties and show early recovery from the induced motor deficits. This study establishes a novel pyramidotomy technique in Sprague Dawley rats that generates persistent motor deficits and has a reduced mortality rate. We used viral neural tracing to identify the course and relative distribution of forelimb and hindlimb motor fibers (n = 9). On basis of the neural tracing data, the medullary pyramid was targeted dorsally from the cerebellar cortex for photothrombotic infarct lesioning (n = 18). The photothrombotic technique selectively destroyed the corticospinal fibers in the medullary pyramid with relative preservation of neighboring grey-matter tissue. MicroPET imaging using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG-microPET) showed a decrease in regional cerebral glucose metabolism (rCGM) in the bilateral pyramid and ipsilateral sensory cortex (p < 0.001, FDR q < 0.05). In addition, the trapezoid bodies and superior olivary nuclei showed a decrease in rCGM, compatible with damage caused during the introduction of the optical fiber. Connected structures such as the inferior colliculi and auditory cortices also showed decreases in rCGM in both hemispheres (p < 0.001, FDR q < 0.05). There was a significant and persistent decrease in motor and sensory function in the contralateral limb following pyramidotomy, as demonstrated by performance in the single pellet reaching task and the foot-fault test. There was no operative mortality or loss of respiratory function in this study. These results indicate that photothrombotic pyramidotomy with a dorsal transcortical approach is a safe and reliable technique for generating a pyramidotomy model with persistent motor deficits.