James W. Fawcett published the review « The extracellular matrix in plasticity and regeneration after CNS injury and neurodegenerative disease » in 2015, highlighting the key role of the chondroitin sulfate proteoglycans (CSPGs) of the extracellular matrix (ECM) in brain plasticity.

CSPGs are present in the brain extracellular matrix and 2% of them are found in perineural nets, a specialized ECM structure responsible for synaptic stabilization in the adult brain.  It was shown in this review that digestion of the CSPGs by enzyme ChABC can greatly increase cerebral plasticity. ChABC could thus help to recover some cerebral function after a stroke, a traumatic brain injury or other forms of brain damage.

In a first study about memory (which is a form of plasticity), object recognition was tested in mice. After ChABC treatment in the perirhinal cortex, memory acquisition was still normal, but memory retention was very much prolonged: when exposed to a novel object during 5 minutes, ChABC treated mice remembered it for 96h, against 12h for untreated mice. The treatment also increased the stimulus/response ratio, suggesting an increased plasticity of connection and an increased number of connections (Romberg et al., 2013).

In an Alzheimer’s disease model, animals who showed complete loss of memory 3h after exposure to a novel object received ChABC to both perirhinal cortices, that fully restored object memory – albeit not permanently (Allen et al., 2002). An other study (Vegh et al., 2014) featuring animals muted to be Alzheimer’s disease models, ChABC injections into the hippocampus could restore two types of memory: contextual memory and long-term potentiation of synapses. An improvement in memory would be highly important to those with memory loss due to a neurodegenerative disease.

The conclusion, as stated in this review, is that ECM modulation could provide a useful treatment for patients with neurodegenerative disease, such as Alzheimer’s disease. It is important to understand how the extracellular matrix controls plasticity, such as memory recovery for example. That is why HCS Pharma developed BIOMIMESYS® Brain, which mimics brain ECM, with the aim to consider it in cerebral in vitro models!

Warm thanks to Rémi Giraudet, engineer-student in AgroPariTech, who wrote this article as part of a bibliographic project about the importance of ECM in brain pathology!


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