Mexiletine treatment-induced inhibition of caspase-3 activation and improvement of behavioral recovery after spinal cord injury.
OBJECTIVE
It has been demonstrated in several experimental studies that apoptosis contributes to cellular damage after spinal cord injury (SCI). During apoptosis dying cells secrete additional mediators of apoptosis such as cytokines and free radicals which have additional toxic effects and exacerbate neuronal death. The aim of this laboratory study was to investigate the effects of mexiletine on caspase-3 activation and functional recovery and compare its post-SCI effectiveness with methylprednisolone.


METHODS
The rats were divided into five groups. Animals in the trauma group underwent traumatic interventions after laminectomy. Spinal cord contusion injury was produced using the weight-drop method. Animals in treatment groups received a single dose of methylprednisolone sodium succinate (Group C), single dose of mexiletine (Group D), or vehicle solution (saline; Group E) intraperitoneally immediately after injury. Hind-limb functions were assessed using the inclined plane technique and caspase-3 activity in tissue samples was measured 24 hours after SCI. Traumatic injury was found to increase tissue caspase-3 activity. In both treatment groups the drug prevented an increase in caspase-3 activity. Mexiletine treatment improved early behavioral recovery after SCI.


CONCLUSIONS
The results obtained in this study demonstrated that mexiletine treatment inhibits caspase-3 activation and preserve/restore better neuronal function compared with methylprednisolone after experimental SCI.
Kaptanoglu
Erkan
E
Department of Neurosurgery, Ankara Numune Education and Research Hospital, Hacettepe University, Ankara, Turkey. erkankaptanoglu@yahoo.com
Caner
Hakan
H
Solaroglu
Ihsan
I
Kilinc
Kamer
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D008775:Methylprednisolone / Q000494:pharmacology; D008801:Mexiletine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D008801:Mexiletine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D008775:Methylprednisolone