Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats.
Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair.
Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
Lei
L
Cheng
Yi
Y
Liu
Hua
H
Zhao
Wen
W
Zhang
Ying-Jun
YJ
Guo
Lin
L
Nie
D000818:Animals; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D016086:Lentivirus; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020127:Recovery of Function / Q000235:genetics; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000503:physiopathology
C577430:CDNF protein, rat; D009414:Nerve Growth Factors
Conserved dopamine neurotrophic factor; Lentiviral vector; Peripheral nerve; Regeneration