MR spectroscopic imaging to detect the development of latent epilepsy

描述（由申请人提供）：磁共振光谱成像（MRSI）已被许多研究小组开发和使用，用于定位人类癫痫的损伤和癫痫发作区域。其成功的内在原因是即使在没有组织体积损失的情况下也常见代谢功能障碍，例如，如MRI阴性的颞叶癫痫病例所示。虽然这种成功的检测是有用的，随后有针对性的癫痫和手术管理，它已经认识到，如果早期检测是可行的和准确的，癫痫的治疗可以大大改变和改善。从人类和动物模型的经验来看，获得性癫痫的病理生理学是由脑损伤（例如，相当常见的发热诱发或热性惊厥、头部创伤或感染事件），随后是在明显的自发性复发性惊厥（“SRS”）发作之前的潜伏期，即，癫痫如果早期检测是可行的，有几种强大的潜在治疗方法可能会降低发展为临床癫痫的可能性（不同的癫痫）。 来自简单地降低癫痫发作可能性的治疗），例如，促红细胞生成素，抗炎化合物，抗氧化剂。在这项研究中，我们研究是否MRSI可以检测到早期癫痫在此潜伏期。我们使用大鼠穿通径刺激（PPS）模型，该模型复制了许多获得性人类内侧颞叶癫痫的定义特征。重要的是，该模型没有显示出在化学惊厥模型中常见的广泛脑损伤。我们从这个24小时PPS模型中获得的初步脑提取物数据显示，在初始损伤后4d，可以看到肌醇、谷氨酰胺、GABA和N-乙酰天冬氨酸的实质性变化。在这个项目中，我们将测试的能力，在体内MRSI检测4天后，刺激损伤损伤的水平和早期癫痫的发展，使用严重和轻度版本的PPS模型。这将以设盲方式进行。由于所有动物也将进行视频和EEG监测，我们还将能够测试MRSI识别那些继续发展明显复发性癫痫发作的动物的能力。

DESCRIPTION (provided by applicant): Magnetic resonance spectroscopic imaging (MRSI) has been developed and used by many groups to localize the regions of injury and seizure onset in human epilepsy. Intrinsic to its success is the common finding of metabolic dysfunction even in the absence of tissue volume loss, e.g., as has been shown in MRI-negative cases of temporal lobe epilepsy. Although this successful detection is useful for subsequent targeted and surgical management of epilepsy, it has been recognized that the treatment of epilepsy could be substantively changed and improved if early detection were feasible and accurate. From both human and animal model experience, the pathophysiology of acquired epilepsy is initiated by a cerebral insult (e.g., the fairly common event of fever-induced or febrile seizures, head trauma or infection), followed by a latent period that precedes the onset of overt spontaneous recurrent seizures ("SRS"), i.e., epilepsy. If early detection were available, there are several strong potential therapeutics that might decrease the likelihood of developing clinical epilepsy (distinct from therapy that simply decreases the likelihood of seizures), e.g., erythropoietin, anti-inflammatory compounds, anti- oxidants. In this study we examine whether MRSI can detect incipient epilepsy during this latent period. We do this using the rat perforant path stimulation (PPS) model, which replicates many of the defining features of acquired human medial temporal lobe epilepsy. Importantly this model does not show widespread brain injury commonly seen in chemoconvulsant models. Our preliminary brain extract data from this 24hour PPS model show that by 4days after initial insult, substantial changes in myo-inositol, glutamine, GABA and N-acetyl aspartate are seen. In this project, we will test the ability of in vivo MRSI to detect 4 das after the stimulation injury the level of injury and the development of incipient epilepsy using a severe and mild version of the PPS model. This will be done in a blinded fashion. As all animals will also be video and EEG monitored, we will also be able to test the ability of the MRSI to identify those animals who go on to develop overt recurrent seizures.