Ultrastructure protection and attenuation of lipid peroxidation after blockade of presynaptic release of glutamate by lamotrigine in experimental spinal cord injury.

Abstract:

OBJECT:Lamotrigine is an antiepileptic drug that inhibits presynaptic voltage-gated sodium channels and reduces the presynaptic release of glutamate in pathological states. Neuroprotective effects of this drug have already been demonstrated in cerebral ischemia models. The aim of the present study was to determine the effects of presynaptic glutamate release inhibition on experimental spinal cord injury (SCI). METHODS:A total of 66 adult Wistar rats were randomly allocated into 6 groups. Group I was the control group used to obtain normal blood samples and spinal cord specimens. Spinal cord injury was introduced by using the extradural clip compression technique, but no medication was given to Group II (trauma group) rats. Group III was treated with vehicle, and the same amount of dimethyl sulfoxide used in treatment groups was administered to these rats. A dose of 50 mg/kg lamotrigine was administered intraperitoneally to Group IV (pretreatment), Group V (peritreatment), and Group VI (posttreatment) rats 30 minutes before, during, and 30 minutes after SCI, respectively. Oxidative stress parameters and transmission electron microscopic findings were examined. RESULTS:Blockade of presynaptic release of glutamate by lamotrigine treatment yielded protective effects on the spinal cord ultrastructure even when administered after the SCI, but it prevented oxidative stress only when it was administered before or during the SCI. CONCLUSIONS:Currently, no available agent has been identified, that can block all the glutamate receptors at the same time. To prevent excitotoxicity in SCI, inhibiting glutamate release from the presynaptic buttons instead of blocking the postsynaptic glutamate receptors seems to be a more rational approach. Further research, such as neurobehavioral assessment, is warranted to demonstrate the probable neuroprotective effects of presynaptic glutamate release inhibition in SCI.

journal_name

Neurosurg Focus

journal_title

Neurosurgical focus

authors

Tufan K,Oztanir N,Ofluoglu E,Ozogul C,Uzum N,Dursun A,Pasaoglu H,Pasaoglu A

doi

10.3171/FOC.2008.25.11.E6

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

E6

issue

5

issn

1092-0684

journal_volume

25

pub_type

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