Hyaluronidase inhibition accelerates functional recovery from stroke in the mouse brain

AbstractPerineuronal nets (PNNs) are presumed to limit plasticity in adult animals. Ischemic 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 altered expression of HA metabolism enzymes. Additionally, we investigated whether early hyaluronidase inhibition interferes with poststroke 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, using quantitative real ‐time polymerase chain reaction and immunofluorescence. Skilled reaching test was employed to test hyaluronidase inhibitor L‐ascorbic acid 6‐hexadecanoate influence on poststroke recovery. We found the simultaneous upregulation of mRNA of HA synthesizing and degrading enzymes in the perilesion al area early after stroke, suggesting acceleration of HA turnover in ischemic animals. Immunostaining revealed differential cellular localization of enzymes, with hyaluronidase 1 in astrocytes and hyaluronan synthase 2 in astrocytes and neurons, and poststroke upregulation of both of them in astroc ytes. β‐glucuronidase was observed in neurons but poststroke upregulation occurred in microglia. Inhibition of hyaluronidase activity ear...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research