Tufan Kadir, Oztanir Namik, Ofluoglu Ebru, Ozogul Candan, Uzum Nuket, Dursun Ayse, Pasaoglu Hatice, Pasaoglu Aydin
Department of Neurosurgery, Gazi University Medical School, Ankara, Turkey.
Neurosurg Focus. 2008;25(5):E6. doi: 10.3171/FOC.2008.25.11.E6.
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).
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.
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.
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.
拉莫三嗪是一种抗癫痫药物，可抑制突触前电压门控钠通道，并在病理状态下减少谷氨酸的突触前释放。该药物的神经保护作用已在脑缺血模型中得到证实。本研究的目的是确定突触前谷氨酸释放抑制对实验性脊髓损伤（SCI）的影响。
总共66只成年Wistar大鼠被随机分为6组。第一组为对照组，用于获取正常血液样本和脊髓标本。采用硬膜外夹压技术造成脊髓损伤，但第二组（创伤组）大鼠不给予药物治疗。第三组用赋形剂治疗，给这些大鼠注射与治疗组相同剂量的二甲基亚砜。第四组（预处理组）、第五组（治疗中组）和第六组（治疗后组）大鼠分别在脊髓损伤前30分钟、损伤期间和损伤后30分钟腹腔注射50mg/kg拉莫三嗪。检测氧化应激参数和透射电子显微镜观察结果。
拉莫三嗪治疗阻断谷氨酸的突触前释放，即使在脊髓损伤后给药，也对脊髓超微结构产生保护作用，但只有在脊髓损伤前或损伤期间给药时才能预防氧化应激。
目前，尚未发现能同时阻断所有谷氨酸受体的药物。为防止脊髓损伤中的兴奋性毒性，抑制突触前纽扣释放谷氨酸而非阻断突触后谷氨酸受体似乎是一种更合理的方法。有必要进行进一步研究，如神经行为评估，以证明突触前谷氨酸释放抑制在脊髓损伤中可能的神经保护作用。
