Corticospinal Sprouting Differs According to Spinal Injury Location and Cortical Origin in Macaque Monkeys

Abstract

The primate corticospinal tract (CST), the major descending pathway mediating voluntary hand movements, comprises nine or more functional subdivisions. The role of subcomponents other than that from primary motor cortex, however, is not well understood. We have previously shown that following a cervical dorsal rhizotomy (Darian-Smith et al., 2013), CST projections originating from primary somatosensory (S1) and motor (M1) cortex responded quite differently to injury. Terminal projections from the S1 (areas 3b/1/2) shrank to Ͻ60% of the contralateral side, while M1 CST projections remained robust or expanded (Ͼ110%). Here, we asked what happens when a central lesion is added to the equation, to better simulate clinical injury. Monkeys (n ϭ 6) received either a unilateral (1) dorsal root lesion (DRL), (2) or a combined DRL/dorsal column lesion (DRL/DCL), or (3) a DRL/DCL where the DCL was made 4 months following the initial DRL. Electrophysiological recordings were made in S1 4 months postlesion in the first two groups, and 6 weeks after the DCL in the third lesion group, to identify the reorganized region of D1-D3 (thumb, index finger, and middle finger) representation. Anterograde tracers were then injected bilaterally to assess spinal terminal labeling. Remarkably, in all DRL/DCL animals, terminal projections from the S1 and M1 extended bilaterally and caudally well beyond terminal territories in normal animals or following a DRL. These data were highly significant. Extensive sprouting from the S1 CST has not been reported previously, and these data raise important questions about S1 CST involvement in recovery following spinal injury.

Extensive somatosensory and motor corticospinal sprouting occurs following a central dorsal column lesion in monkeys

“…Here, we observed a significant bilateral expansion of the terminal territory into the intermediate zone and ventral horn. This was also similar to, but not as extensive as that seen in monkeys with a combined DRL/DCL (Darian‐Smith et al, ). Terminal boutons were found rostrocaudally in segments extending from C1–T2 (M1401 = 37.9 mm, M1403 = 49.7 mm), or almost 1.5 segments beyond the range observed in “normal” (i.e., labeling in DRL contralateral to the lesion) monkeys, but terminal sprouting stopped two segments short of the most caudal labeling observed in animals that received a combined DRL/DCL (Figures , and ).…”

“…Dorsal column lesions were highly consistent between animals and limited to the cuneate fasciculus (see, Figure a,b for DCL only and Figure e for DRL/DCL; Darian‐Smith et al, ). There may have been minor sparing of the cuneate fasciculus medially, which is topographically associated with input from more radial (i.e., D5) hand regions.…”

Leveraging biomedical informatics for assessing plasticity and repair in primate spinal cord injury

“…A recent study in non-human primates revealed a novel finding of sprouting of the CST from the primary somatosensory cortex, in addition to the primary motor cortex, after a combined peripheral and spinal lesion (Darian-Smith et al, 2014). This study raises the important question about the role of the primary somatosensory cortex in CST plasticity following SCI.…”

“…Our aim is to better understand the intrinsic nature of SCI in non-human primates, and to complement research being done by other groups to optimize therapeutics for clinical application in humans. Previous studies by others have assessed a wide range of important aspects of this translational model, including cortical reorganization and contribution to recovery (Chen et al, 2012; Darian-Smith et al, 2014; Qi et al, 2011), mechanisms of degeneration (Shi et al, 2009; Wu et al, 2013), and cell-therapy transplantation studies (Levi et al, 2002; Nemati et al, 2014). The overarching goal of the CSCC is to integrate as much complementary information as possible in a single translational model.…”

Rigor or Mortis: Best Practices for Preclinical Research in Neuroscience

“…But there are situations where numbers of animals are intentionally kept small for ethical reasons (for example, studies involving primates). There are statistical approaches to this problem, for example, using a repeated-measures statistic design where different samples from a single subject (for example different sections) are treated as a repeated measure (Darian-Smith et al, 2014). Enhancing rigor for studies with small numbers of animals that would otherwise be underpowered may require developing new statistical tools with nested designs.…”