Abstract | BACKGROUND: METHODS: Thirty Wistar albino rats were divided into 3 groups of 10 each: the sham-operated controls (group 1), the trauma-created controls (group 2), and the QVD- OPh-treated rats (group 3). An SCI (a trauma of 40 g-cm) was produced at the thoracic level (T8-T10) by the weight-drop technique. The response to injury and the neuroprotective effects of Q-VD-OPh were investigated by histopathologic examination and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) 24 hours and 5 days after trauma. The inclined plane technique of Rivlin and Tator and a modified version of Tarlov's grading scale were used to assess the functional status of the rats 24 hours, 3 days, and 5 days after injury. RESULTS: Twenty-four hours after trauma, light microscopic examination of a specimen taken from group 2 rats revealed hemorrhage, necrosis, vascular thrombi, and edema. Group 3 tissue samples showed similar features at that time. Twenty-four hours after trauma, the mean apoptotic cell number was 4.47 +/- 0.35 cells in group 2 and 1.58 +/- 0.33 in group 3. Five days after injury, the mean apoptotic cell count was 4.35 +/- 0.47 in group 2 and 1.25 +/- 0.34 in group 3. Thus the number of TUNEL-positive cells in an injured spinal cord was greatly reduced by treatment with Q-VDOPh. The neurologic function scores (both the inclined plane performance and motor grading scores) were significantly better in the Q-VD-OPh-treated group than in the trauma-created control group. CONCLUSION: The marked antiapoptotic properties of Q-VD-OPh due to the inhibition of all caspases render it a promising novel agent. A therapeutic strategy using Q-VD-OPh may eventually lead to the effective treatment of SCI in humans.
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Authors | A Colak, V Antar, A Karaoğlan, O Akdemir, E Sahan, O Celik, A Sağmanligil |
Journal | Neurocirugia (Asturias, Spain)
(Neurocirugia (Astur))
Vol. 20
Issue 6
Pg. 533-40; discussion 540
(Dec 2009)
ISSN: 1130-1473 [Print] Spain |
PMID | 19967318
(Publication Type: Journal Article)
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Chemical References |
- Amino Acid Chloromethyl Ketones
- Caspase Inhibitors
- Quinolines
- quinoline-val-asp(OMe)-CH2-OPH
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Topics |
- Amino Acid Chloromethyl Ketones
(pharmacology)
- Animals
- Apoptosis
(drug effects)
- Caspase Inhibitors
- Hindlimb
(pathology)
- In Situ Nick-End Labeling
- Male
- Quinolines
(pharmacology)
- Rats
- Rats, Wistar
- Recovery of Function
(drug effects)
- Spinal Cord
(cytology, drug effects, enzymology, pathology)
- Spinal Cord Injuries
(enzymology, pathology, physiopathology)
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