Abstract

The corticospinal tract (CST) is an essential neural pathway for reorganization that recovers motor functions after brain injuries such as stroke. CST comprises multiple pathways derived from different sensorimotor areas of the cerebral cortex; however, the patterns of reorganization in such complex pathways postinjury are largely unknown. Here we comprehensively examined the rewiring patterns of the CST pathways of multiple cerebral origins in a mouse stroke model that varied in size and location in the sensorimotor cortex. We found that spared contralesional motor and sensory CST axons crossed the midline and sprouted into the denervated side of the cervical spinal cord after stroke in a large cortical area. In contrast, the contralesional CST fibers did not sprout in a small stroke, whereas the ipsilesional axons from the spared motor area grew on the denervated side. We further showed that motor and sensory CST axons did not innervate the projecting areas mutually when either one was injured. The present results reveal the basic principles that generate the patterns of CST rewiring, which depend on stroke location and CST subtype. Our data indicate the importance of targeting different neural substrates to restore function among the types of injury.

Highlights

  • Brain injuries such as stroke and trauma lead to neurological deficits that frequently impair motor and sensory functions

  • We assessed the completeness of the lesions by comparing the lesion area with the coordinates of rostral forelimb area (RFA)/caudal forelimb area (CFA)/primary somatosensory cortex (S1) areas that we previously determined by retrograde tracing of corticospinal tract (CST) neurons (Figure 1C; Ueno et al, 2018)

  • We confirmed that strokeRFA+CFA+S1 and strokeCFA+S1 induced deficits in skilled forelimb reaching in other sets of animals

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Summary

Introduction

Brain injuries such as stroke and trauma lead to neurological deficits that frequently impair motor and sensory functions. One of the factors affecting the recovery process is the location and volume of the lesion (Alexander et al, 2010; Grefkes and Ward, 2014; Isa et al, 2019; Karthikeyan et al, 2019; Aswendt et al, 2021). This suggests that the location and size of spared brain areas are the determinants of recovery, in which their circuits might be differentially reorganized in each case. The heterogeneity of lesion location makes it challenging to systematically understand or predict the recovery process and its Abbreviations: BDA, biotinylated dextran amine; CFA, caudal forelimb area; CST, corticospinal tract; M1, primary motor cortex; RFA, rostral forelimb area; S1, primary somatosensory cortex

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