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Updated: Jul 29, 2026
Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia
Published on: July 22, 2017
Cyclin D1 and Cdk4 protein induction in motor neurons after transient spinal cord ischemia in rabbits
1Department of Thoracic Surgery, Tohoku University School of Medicine, Sendai, Japan.
Background And Purpose:
The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells against ischemia. However, the mechanisms of such vulnerability are not fully understood. We hypothesized that spinal motor neurons might be lost by programmed cell death and investigated a possible mechanism of neuronal death by detection of double-strand breaks in genomic DNA and immunohistochemical analysis for cyclin D1 and cyclin-dependent kinases (Cdk) 4.
Methods:
We used a rabbit spinal cord ischemia model with a balloon catheter. Spinal cord was removed at 8 hours and 1, 2, and 7 days after 15 minutes of transient ischemia, and histological changes were studied with hematoxylin-eosin staining. In situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL), DNA fragment with gel electrophoresis, Western blot analysis for cyclin D1 and Cdk4, and temporal profiles of cyclin D1 and Cdk4 immunoreactivity were investigated.
Results:
Most motor neurons were preserved until 2 days but were selectively lost at 7 days of reperfusion. Immunocytochemistry showed positive TUNEL selectively at 2 days of reperfusion in spinal motor neuron nuclei. Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunoreactivity of cyclin D1 and Cdk4 proteins was induced selectively at 8 hours in motor neuron nuclei, which eventually died.
Conclusions:
These results indicate that induction of cyclin D1 and Cdk4 may be implicated in programmed cell death change after transient spinal cord ischemia in rabbits.
Insights
Spinal motor neurons undergo programmed cell death following ischemia, evidenced by DNA damage. This cell death involves the induction of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in vulnerable neurons.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Spinal cord injury mechanisms are linked to motor neuron vulnerability during ischemia.
- The precise mechanisms driving this vulnerability remain unclear.
Purpose of the Study:
- To investigate programmed cell death in spinal motor neurons after transient ischemia.
- To explore the role of DNA damage, cyclin D1, and Cdk4 in this process.
Main Methods:
- A rabbit model of transient spinal cord ischemia was utilized.
- Histological analysis, TUNEL assay, DNA fragmentation, and Western blotting for cyclin D1 and Cdk4 were performed.
Main Results:
- Motor neurons were selectively lost 7 days post-ischemia.
- DNA fragmentation and positive TUNEL staining indicated programmed cell death.
- Cyclin D1 and Cdk4 expression increased in motor neuron nuclei prior to cell death.
Conclusions:
- The induction of cyclin D1 and Cdk4 is associated with programmed cell death in spinal motor neurons after transient ischemia.
- These findings suggest a potential therapeutic target for spinal cord injury.
