Neuroprotective effects of Ac.YVAD.cmk on experimental spinal cord injury in rats.
BACKGROUND
Apoptosis as a cell death mechanism is important in numerous diseases, including traumatic SCI. We evaluated the neuroprotective effects of Ac.YVAD.cmk and functional outcomes in a rat SCI model.


METHODS
Thirty rats were randomized into 3 groups of 10: sham-operated, trauma only, and trauma plus Ac.YVAD.cmk treatment. Trauma was produced in the thoracic region by a weight-drop technique. Group 3 rats received Ac.YVAD.cmk (1 mg/kg, ip) 1 minute after trauma. The rats were killed at 24 hours and 5 days after injury. Efficacy was evaluated with light microscopy and TUNEL staining. Functional outcomes were assessed with the inclined plane technique and a modified version of the Tarlov grading system.


RESULTS
At 24 hours postinjury, the respective mean number of apoptotic cells in groups 1, 2, and 3 were 0, 5.26 +/- 0.19, and 0.97 +/- 0.15. Microscopic examination of group 2 tissues showed widespread hemorrhage, edema, necrosis, and polymorphic nuclear leukocyte infiltration and vascular thrombi. Group 3 tissues revealed similar features, but cavitation and demyelination were less prominent than those in group 2 samples at this period. At 5 days postinjury, the respective mean inclined plane angles in groups 1, 2, and 3 were 65.5 +/- 2.09, 42.00 +/- 2.74, and 52.5 +/- 1.77. Motor grading of animals revealed a similar trend. These differences were statistically significant (P < .05).


CONCLUSIONS
Ac.YVAD.cmk inhibited posttraumatic apoptosis in a rat SCI model. This may provide the basis for development of new therapeutic strategies for the treatment of SCI.
Karaoğlan
Alper
A
Clinic of Neurosurgery, Taksim Education and Research Hospital, Istanbul, Turkey.
Kaya
Ekrem
E
Akdemir
Osman
O
Sağmanligil
Ayhan
A
Bilguvar
Kaya
K
Cirakoğlu
Beyazýt
B
Sahan
Elife
E
Erdoğan
Nusret
N
Barut
A Eref
AE
Colak
Ahmet
A
D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D020287:In Situ Nick-End Labeling; D009043:Motor Activity; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone