Protracted Morphological Changes in the Corticospinal Tract Within the Cervical Spinal Cord After Intracerebral Hemorrhage in the Right Striatum of Mice.

Anson Cho Kiu Ng,Jing Li,Haitao Sun,Min Yao,Stephen Yin Cheng,Jian-Dong Huang,Wutian Wu,Gilberto Ka Kit Leung

doi:10.3389/fnins.2020.00506

Abstract

Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality rates. Currently, there is no promising treatment that improves prognosis significantly. While a thorough investigation of the pathological process within the primary site of injury in the brain has been conducted by the research field, the focus was mainly on gray matter injury, which partly accounted for the failure of discovery of clinically efficacious treatments. It is not until recent years that white matter (WM) injury in the brain after subcortical ICH was examined. As WM tracts form networks between different regions, damage to fibers should impair brain connectivity, resulting in functional impairment. Although WM changes have been demonstrated in the brain after ICH, alterations distant from the initial injury site down in the spinal cord are unclear. This longitudinal study, for the first time, revealed prolonged morphological changes of the contralesional dorsal corticospinal tract (CST) in the spinal cord 5 weeks after experimental ICH in mice by confocal microscopy and transmission electron microscopy, implying that the structural integrity of the CST was compromised extensively after ICH. Given the important role of CST in motor function, future translational studies targeting motor recovery should delineate the treatment effects on CST integrity.

Highlights

Intracerebral hemorrhage (ICH) damages gray matter, as well as white matter (WM) (Tao et al, 2017; Zuo et al, 2017)
The present study provided the evidence of prolonged damage to the contralesional dorsal corticospinal tract (CST) in the cervical spinal cords of adult wild-type mice after intrastriatal collagenase injection, a commonly used ICH model
The injury to the right hemisphere led to obvious derangement of WM on the left side of the cervical spinal cord, which persisted for at least 5 weeks after ICH [Figure 3A(ii–vi)]

Summary

Introduction

Intracerebral hemorrhage (ICH) damages gray matter, as well as white matter (WM) (Tao et al, 2017; Zuo et al, 2017). Clinical studies have looked into the association between WM tract integrity and functional recovery at different time points and locations after stroke, motor outcomes (Jang et al, 2010). The structural changes of the CST in the ipsilesional hemisphere down to the contralesional medullary pyramid during acute and chronic phases, as demonstrated in patients by neuroimaging, correlate with motor recovery. This could possibly be used for outcome prediction after ICH (Cho et al, 2007; Yoshioka et al, 2008; Kusano et al, 2009; Jang et al, 2010; Jayaram et al, 2012; Venkatasubramanian et al, 2013). An animal study provided direct histological evidence of secondary substantia nigra and CST changes in the brain for up to 4 months after experimental ICH (Fan et al, 2013)

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Conclusion