Epilepsy Centre, Department of Clinical Sciences, Lund University, Lund University Hospital, SE-22362, Lund, Sweden.
Neurosurgery, Department of Clinical Sciences, Lund University, Skånes Universitetssjukhus, SE-22362, Lund, Sweden.
Sci Rep. 2019 Dec 18;9(1):19393. doi: 10.1038/s41598-019-56062-1.
In epilepsy patients, drug-resistant seizures often originate in one of the temporal lobes. In selected cases, when certain requirements are met, this area is surgically resected for therapeutic reasons. We kept the resected tissue slices alive in vitro for 48 h to create a platform for testing a novel treatment strategy based on neuropeptide Y (NPY) against drug-resistant epilepsy. We demonstrate that NPY exerts a significant inhibitory effect on epileptiform activity, recorded with whole-cell patch-clamp, in human hippocampal dentate gyrus. Application of NPY reduced overall number of paroxysmal depolarising shifts and action potentials. This effect was mediated by Y2 receptors, since application of selective Y2-receptor antagonist blocked the effect of NPY. This proof-of-concept finding is an important translational milestone for validating NPY-based gene therapy for targeting focal drug-resistant epilepsies, and increasing the prospects for positive outcome in potential clinical trials.
在癫痫患者中，耐药性癫痫发作通常起源于一个颞叶。在某些特定情况下，当满足某些要求时，出于治疗原因，会对该区域进行手术切除。我们将切除的组织切片在体外保存 48 小时，以创建一个基于神经肽 Y（NPY）治疗耐药性癫痫的新治疗策略的测试平台。我们证明，NPY 对全细胞膜片钳记录的人类海马齿状回癫痫样活动具有显著的抑制作用。NPY 的应用减少了阵发性去极化转移和动作电位的总数。这种作用是由 Y2 受体介导的，因为选择性 Y2 受体拮抗剂的应用阻断了 NPY 的作用。这一概念验证发现是验证基于 NPY 的基因治疗针对局灶性耐药性癫痫的重要转化里程碑，并增加了在潜在临床试验中取得积极结果的前景。
