Protecting white matter is one of the key treatment strategies for
spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination.
Rapamycin has been shown
neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of
rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of
rapamycin in neuroprotection after hemi-
contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the
rapamycin group (n = 16), vehicle group (n = 16), and
sham group (n = 10). All mice of the
rapamycin and vehicle groups received a unilateral
contusion with 1.2-mm displacement at C5 followed by daily
intraperitoneal injection of
rapamycin or
dimethyl sulfoxide solution (1.5 mg⋅kg-1⋅day-1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The
autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the
glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm
contusion led to a consistent moderate-severe SCI in terms of motor function and tissue damage.
Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the
glial scar at the epicenter. Additionally,
rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the
rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and
weight loss. Our results suggest that
rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce
glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.