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Neurochem Int. 2012 Dec;61(7):963-72. doi: 10.1016/j.neuint.2012.08.007. Epub 2012 Aug 29.

The perineuronal net component of the extracellular matrix in plasticity and epilepsy.

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Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.


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.

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