Hyaluronidase inhibition accelerates functional recovery from stroke in the mouse brain

Hyaluronic acid (HA) is the main component of the brain extracellular matrix (ECM). During stroke, a massive breakdown of HA occurs (including perineuronal net ‐associated HA), however, the mechanism of this phenomenon remains unclear. We hypothesized that stroke up‐regulates the expression of HA metabolism‐associated enzymes and increases HA synthesis/degradation. We observed increased expression of HA‐degrading hyaluronidases and hexosaminidases, as well as HA synthases. Immunofluorescence studies revealed predominating astrocytic origin of the enzymes. Moreover, we found that inhibiting hyaluronidases with Vcpal resulted in improved behavioural outcome, even though PNNs were not protected, possibly by attenuating neuropil HA breakage. AbstractPerineuronal nets (PNNs) are presumed to limit plasticity in adult animals. Ischaemic stroke results in the massive breakdown of PNNs resulting in rejuvenating states of neuronal plasticity, but the mechanisms of this phenomenon are largely unknown. As hyaluronic acid (HA) is the structural backbone of PNNs, we hypothesized that these changes are a consequence of the altered expression of HA metabolism enzymes. Additionally, we investigated whether early hyaluronidase inhibition interferes with post ‐stroke PNN reduction and behavioural recovery. We investigated the mRNA/protein expression of these enzymes in the perilesional, remote and contralateral cortical regions in mice at different time points after photothrombosis, u...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research