Calpain inhibitor AK 295 inhibits calpain-induced apoptosis and improves neurologic function after traumatic spinal cord injury in rats

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dc.authorid0000-0002-4713-4271en_US
dc.contributor.authorÇolak A.
dc.contributor.authorKaya M.
dc.contributor.authorKaraoglan A.
dc.contributor.authorSagmanligil A.
dc.contributor.authorAkdemir O.
dc.contributor.authorŞahan E.
dc.contributor.authorÇelik Ö.
dc.date.accessioned2024-07-12T21:52:26Z
dc.date.available2024-07-12T21:52:26Z
dc.date.issued2009en_US
dc.departmentMaltepe Üniversitesien_US
dc.description.abstractBackground. An increase in the level of intracellular calcium activates the calcium-dependent neutral protease calpain, which in turn leads to cellular dysfunction and cell death after an insult to the central nervous system. In this study, we evaluated the effect of a calpain inhibitor, AK 295, on spinal cord structure, neurologic function, and apoptosis after spinal cord injury (SCI) in a murine model. 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 calpain-dependent 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.en_US
dc.identifier.doi10.1016/S1130-1473(09)70163-0
dc.identifier.endpage254en_US
dc.identifier.issn1130-1473
dc.identifier.issue3en_US
dc.identifier.pmid19575128en_US
dc.identifier.scopus2-s2.0-70349766092en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage245en_US
dc.identifier.urihttps://dx.doi.org/10.1016/S1130-1473(09)70163-0
dc.identifier.urihttps://hdl.handle.net/20.500.12415/8370
dc.identifier.volume20en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherSociedad Espanola de Neurocirugiaen_US
dc.relation.ispartofNeurocirugiaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKY03093
dc.subjectAK 295en_US
dc.subjectApoptosisen_US
dc.subjectCalpain inhibitoren_US
dc.subjectSecondary damageen_US
dc.subjectSpinal cord traumaen_US
dc.titleCalpain inhibitor AK 295 inhibits calpain-induced apoptosis and improves neurologic function after traumatic spinal cord injury in ratsen_US
dc.typeArticle
dspace.entity.typePublication

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