Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

Abstract

Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity-dependent and homeostatic plasticity, suggests that microglia-mediated pro- and/or anti-inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

“…At the same time myelin-associated growth inhibitors are released through exosomes from oligodendrocytes [ 195 ]. Therefore, active production of exosomes in the injuries areas of CNS may have a strong effect on CNS neuroplasticity, including collateral sprouting and unmasking of latent synapses [ 196 , 197 ].…”

Post-Ischaemic Immunological Response in the Brain: Targeting Microglia in Ischaemic Stroke Therapy

“…Microglia also contribute to the maintenance of homeostasis within the CNS, including promoting neuronal survival and mediating synaptic plasticity [24,25]. These roles involve the secretion of trophic factors, e.g., brain-derived neurotrophic factor (BDNF) [26,27], insulin-like growth factor-1 (IGF-1) [28] and pruning of neuronal synapses, which involves complement factor C1q [29][30][31]. Microglia also remodel the extracellular matrix through the secretion of several proteolytic enzymes, such as matrix metalloproteases (MMPs) and tissue-type plasminogen activator (tPA) [28].…”

Gene Expression Dynamics at the Neurovascular Unit During Early Regeneration After Cerebral Ischemia/Reperfusion Injury in Mice

“…Previous experimental studies have shown a neuroprotective effect of acute MMP-9 inhibition in stroke (Asahi et al, 2000) whereas MMP-9 inhibition in the early recovery phase exacerbated stroke-induced brain damage (Zhao et al, 2006). Several other pathophysiological processes have shown a similar unexpected biphasic function after stroke (Ma et al, 2017;Sandvig et al, 2018). Only long-term observations of cohorts with acceptable survival rates allow to assess the full picture of postischemic vascular inflammation, its resolution and tissue repair.…”