Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Neurochem Int. 2012 Dec;61(7):963-72. doi: 10.1016/j.neuint.2012.08.007. Epub 2012 Aug 29.
During development the extracellular matrix (ECM) of the central nervous system (CNS) facilitates proliferation, migration, and synaptogenesis. In the mature nervous system due to changes in the ECM it provides structural stability and impedes proliferation, migration, and synaptogensis. The perineuronal net (PN) is a specialized ECM structure found primarily surrounding inhibitory interneurons where it forms a mesh-like structure around points of synaptic contact. The PN organizes the extracellular space by binding multiple components of the ECM and bringing them into close proximity to the cell membrane, forming dense aggregates surrounding synapses. The PN is expressed late in postnatal development when the nervous system is in the final stages of maturation and the critical periods are closing. Once fully expressed the PN envelopes synapses and leads to decreased plasticity and increases synaptic stability in the CNS. Disruptions in the PN have been studied in a number of disease states including epilepsy. Epilepsy is one of the most common neurologic disorders characterized by excessive neuronal activity which results in recurrent spontaneous seizures. A shift in the delicate balance between excitation and inhibition is believed to be one of the underlying mechanisms in the development of epilepsy. During epileptogenesis, the brain undergoes numerous changes including synaptic rearrangement and axonal sprouting, which require structural plasticity. Because of the PNs location around inhibitory cells and its role in limiting plasticity, the PN is an important candidate for altering the progression of epilepsy. In this review, an overview of the ECM and PN in the CNS will be presented with special emphasis on potential roles in epileptogenesis.
在中枢神经系统（CNS）的发育过程中，细胞外基质（ECM）促进增殖、迁移和突触发生。在成熟的神经系统中，由于 ECM 的变化，它提供了结构稳定性，并阻碍了增殖、迁移和突触发生。周细胞外基质网（PN）是一种特殊的 ECM 结构，主要存在于抑制性中间神经元周围，形成一种围绕突触接触点的网状结构。PN 通过结合 ECM 的多个成分并将它们带到细胞膜附近，形成围绕突触的密集聚集体，从而组织细胞外空间。PN 在出生后发育的后期表达，此时神经系统处于成熟的最后阶段，关键期即将结束。PN 一旦完全表达，就会包裹突触，导致 CNS 中的可塑性降低和突触稳定性增加。PN 的破坏在许多疾病状态中都有研究，包括癫痫。癫痫是最常见的神经系统疾病之一，其特征是神经元活动过度，导致反复自发性癫痫发作。兴奋性和抑制性之间微妙平衡的转变被认为是癫痫发展的潜在机制之一。在癫痫发生过程中，大脑会经历许多变化，包括突触重排和轴突发芽，这需要结构可塑性。由于 PN 位于抑制性细胞周围及其在限制可塑性方面的作用，PN 是改变癫痫进展的重要候选者。在这篇综述中，将介绍 CNS 中的 ECM 和 PN，并特别强调它们在癫痫发生中的潜在作用。
