Abstract | BACKGROUND: METHODS: Thirty albino Wistar rats were divided into 3 groups of 10 each: the sham-operated control group (group 1), the spinal cord trauma group (group 2), and the spinal cord trauma plus AK 295 treatment group (group 3). After having received a combination of ketamine 60 mg/kg and xylazine 9 mg/kg to induce anesthesia, the rats in groups 2 and 3 were subjected to thoracic trauma by the weight drop technique (40 g-cm). One hour after having been subjected to that trauma, the rats in groups 2 and 3 were treated with an intraperitoneal injection of either dimethyl sulfoxide 2 mg/kg or AK 295 2 mg/kg. The effects of the injury and the efficacy of AK 295 were determined by an assessment of the TUNEL technique and the results of examination with a light microscope. The neurologic performance of 5 rats from group 2 and 5 from group 3 was assessed by means of the inclined plane technique and the modified Tarlov's motor grading scale 1, 3, and 5 days after spinal cord trauma. FINDINGS: Light-microscopic examination of spinal cord specimens from group 2 revealed hemorrhage, edema, necrosis, and vascular thrombi 24 hours after trauma. Similar (but less prominent) features were seen in specimens obtained from group 3 rats. Twenty-four hours after injury, the mean apoptotic cell numbers in groups 1 and 2 were zero and 4.57 +/- 0.37 cells, respectively. In group 3, the mean apoptotic cell number was 2.30 +/- 0.34 cells, a value significantly lower than that in group 2 (P < .05). Five days after trauma, the injured rats in group 2 demonstrated significant motor dysfunction (P < .05). In comparison, the motor scores exhibited by group 3 rats were markedly better (P < .05). CONCLUSIONS:
AK 295 inhibited apoptosis via calpaindependent pathways and provided neuroprotection and improved neurologic function in a rat model of SCI. To our knowledge, this is the first study to evaluate the use of AK 295, a calpain inhibitor, after SCI. Our data suggest that AK 295 might be a novel therapeutic compound for the neuroprotection of tissue and the recovery of function in patients with a SCI.
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Authors | A Colak, M Kaya, A Karaoğlan, A Sağmanligil, O Akdemir, E Sahan, O Celik |
Journal | Neurocirugia (Asturias, Spain)
(Neurocirugia (Astur))
Vol. 20
Issue 3
Pg. 245-54
(Jun 2009)
ISSN: 1130-1473 [Print] Spain |
PMID | 19575128
(Publication Type: Journal Article)
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Chemical References |
- Dipeptides
- Neuroprotective Agents
- AK 295
- Calpain
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Topics |
- Animals
- Apoptosis
(drug effects)
- Calpain
(antagonists & inhibitors, metabolism)
- Dipeptides
(pharmacology, therapeutic use)
- Humans
- Motor Activity
(physiology)
- Neuroprotective Agents
(pharmacology, therapeutic use)
- Random Allocation
- Rats
- Rats, Wistar
- Recovery of Function
(drug effects)
- Spinal Cord
(anatomy & histology, drug effects, pathology)
- Spinal Cord Injuries
(drug therapy, pathology)
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