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- W3044804316 abstract "Abstract Vascular damage, central nervous system (CNS) injury, seizure or even psychological stress may trigger activation of microglia and infiltration of other immune cells, accompanied by high levels of expression and activity of extracellular proteases, such as matrix metalloproteinases (MMPs), and degradation/remodelling of the perivascular and perineuronal extracellular matrix (ECM). This acute response is followed by the recovery/chronic phase, during which the activation of astrocytes leads to the upregulated synthesis of ECM molecules, which, in combination with elevated expression of tissue inhibitor of metalloproteinases (TIMP) proteins, increases the aggregation of ECM molecules. This biphasic dysregulation of local balance between extracellular proteases and the ECM activates multiple temporally overlapping signalling cascades, involving receptor‐type protein tyrosine phosphatases, integrins, Toll‐like receptors, cell adhesion molecules, and ion channels, resulting in impaired synaptic plasticity and cognition. An additional level of complexity is related to the leakage of blood plasma proteins, such as fibrinogen, and the diffusion of perivascularly overproduced MMPs, TIMPs and ECM molecules into the CNS parenchyma, leading to diverse effects on neurons and incorporation of these molecules into the interstitial neural ECM. This review aims to outline these complex common mechanisms in stroke, CNS injury, depression, epilepsy, multiple sclerosis and cerebral small vessel disease and to discuss translational strategies to advance the development of new therapies for these neurological and psychiatric diseases." @default.
- W3044804316 created "2020-07-29" @default.
- W3044804316 creator A5028488966 @default.
- W3044804316 creator A5068907567 @default.
- W3044804316 creator A5086875951 @default.
- W3044804316 creator A5089694789 @default.
- W3044804316 creator A5090278762 @default.
- W3044804316 date "2020-07-25" @default.
- W3044804316 modified "2023-10-13" @default.
- W3044804316 title "Interplay between perivascular and perineuronal extracellular matrix remodelling in neurological and psychiatric diseases" @default.
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