Anti-apoptotic effect of insulin in the control of cell death and neurologic deficit after acute spinal cord injury in rats.
Recent studies confirmed that the new cell survival signal pathway of Insulin-PI3K-Akt exerted cyto-protective actions involving anti-apoptosis. This study was undertaken to investigate the potential neuroprotective effects of insulin in the pathogenesis of spinal cord injury (SCI) and evaluate its therapeutic effects in adult rats. SCI was produced by extradural compression using modified Allen's stall with damage energy of 40 g-cm force. One group of rats was subjected to SCI in combination with the administration of recombinant human insulin dissolved in 50% glucose solution at the dose of 1 IU/kg day, for 7 days. At the same time, another group of rats was subjected to SCI in combination with the administration of an equal volume of sterile saline solution. Functional recovery was evaluated using open-field walking, inclined plane tests, and motor evoked potentials (MEPs) during the first 14 days post-trauma. Levels of protein for B-cell lymphoma/leukemia-2 gene (Bcl-2), Caspase-3, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified in the injured spinal cord by Western blot analysis. Neuronal apoptosis was detected by TUNEL, and spinal cord blood flow (SCBF) was measured by laser-Doppler flowmetry (LDF). Ultimately, the data established the effectiveness of insulin treatment in improving neurologic recovery, increasing the expression of anti-apoptotic bcl-2 proteins, inhibiting caspase-3 expression decreasing neuronal apoptosis, reducing the expression of proinflammatory cytokines iNOS and COX-2, and ameliorating microcirculation of injured spinal cord after moderate contusive SCI in rats. In sum, this study reported the beneficial effects of insulin in the treatment of SCI, with the suggestion that insulin should be considered as a potential therapeutic agent.
Wu
Xing-Huo
XH
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang
Shu-Hua
SH
Duan
De-Yu
DY
Cheng
Heng-Hui
HH
Bao
Yu-Ting
YT
Zhang
Yukun
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D007328:Insulin; D018696:Neuroprotective Agents; D011994:Recombinant Proteins