Rapid volume pulsations of the extracellular space accompany epileptiform activity in trauma-injured neocortex and depend on the sodium-bicarbonate cotransporter NBCe1

IF 2 4区医学 Q3 CLINICAL NEUROLOGY Epilepsy Research Pub Date : 2024-03-01 DOI:10.1016/j.eplepsyres.2024.107337

Anthony R. Fringuello , Robert Colbourn , Jeffrey H. Goodman , Hillary B. Michelson , Douglas S.F. Ling , Sabina Hrabetova

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Abstract

Post traumatic epilepsy (PTE) is a treatment-resistant consequence of traumatic brain injury (TBI). Recently, it has been revealed that epileptiform activity in acute chemoconvulsant seizure models is accompanied by transient shrinkages of extracellular space (ECS) called rapid volume pulsations (RVPs). Shrinkage of the ECS surrounding neurons and glia may contribute to ictogenic hyperexcitability and hypersynchrony during the chronic phase of TBI. Here, we identify the phenomenon of RVPs occurring spontaneously in rat neocortex at ≥ 3 weeks after injury in the controlled cortical impact (CCI) model for PTE. We further report that blocking the electrogenic action of the astrocytic cotransporter NBCe1 with 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS) eliminates both RVPs and epileptiform activity in ex-vivo CCI neocortical brain slices. We conclude that NBCe1-mediated extracellular volume shrinkage may represent a new target for therapeutic intervention in PTE.

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细胞外空间的快速体积脉冲伴随着创伤性神经皮质的癫痫样活动，并依赖于钠-碳酸氢盐共转运体 NBCe1

创伤后癫痫（PTE）是创伤性脑损伤（TBI）的一种抗药性后果。最近，有研究发现，在急性化学惊厥发作模型中，痫样活动伴随着被称为快速容积脉动（RVPs）的细胞外空间（ECS）的短暂收缩。神经元和胶质细胞周围 ECS 的收缩可能会导致创伤性脑损伤慢性阶段的致痫高兴奋性和超同步性。在这里，我们在受控皮质冲击（CCI）PTE 模型中发现了大鼠新皮质在损伤后≥ 3 周时自发发生的 RVPs 现象。我们进一步报告说，用 4,4′-二异硫氰基-2,2′-二苯乙烯二磺酸（DIDS）阻断星形胶质细胞共转运体 NBCe1 的电原作用可消除体内外 CCI 新皮质脑切片中的 RVPs 和癫痫样活动。我们的结论是，NBCe1 介导的细胞外容积缩小可能是治疗 PTE 的一个新靶点。

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.