Transient global cerebral ischemia induces rapid and sustained reorganization of synaptic structures

Abstract

Ischemia can cause rapid neuronal damage. Previous studies have suggested that synaptic structures and cortical functions can be rescued if therapeutic interventions are applied in time, but the structural basis for this resilience remains incompletely understood. Here, we investigated the restoration of synaptic structures and postischemic plasticity of dendritic spines in the somatosensory cortices of mice by taking advantage of a reversible global cerebral ischemia model. Intravital two-photon imaging revealed that although dendritic structures were rapidly distorted after global ischemia, only a small percentage of spines were actually lost after transient ischemia. Electron microscopy indicated that most presynaptic electron-dense structures were still apposed to postsynaptic densities, and that the majority of disrupted synaptic structures were rapidly reinstated following reperfusion after transient ischemia. Repeated imaging suggested that restored dendrites survived the initial ischemia -reperfusion challenge. Importantly, spines on the restored dendrites underwent a rapid and sustained structural reorganization following transient ischemia. These findings suggested that disrupted synapses during transient ischemia could be rapidly restored after ischemia/reperfusion, and that restored dendritic structures remained plastic to rebuild the cortical network.

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

“…It was shown that postischemic changes in the SR layer of the hippocampus are limited to the region of synaptic terminals (clumping or dispersion of the synaptic vesicle pools and damage to synaptic membranes) and synaptic terminals are the primary and early target in the development of damage to the postischemic neurons [ 14 , 26 ]. It is suggested that a close relationship with the processes of neurons reflects the participation of Rod microglia in synaptic stripping and neuronal circuitry reorganization [ 56 , 59 ]. The study of microglia-synaptic interactions showed that there is not complete destruction of the synapses, but selective partial phagocytosis or trogocytosis, of presynaptic structures [ 60 ].…”

Increased BBB Permeability Enhances Activation of Microglia and Exacerbates Loss of Dendritic Spines After Transient Global Cerebral Ischemia

“…Among these diseases, stroke can rapidly cause disruption of BBB. Severe stroke can lead to blood vessel damage and drastic BBB leakage within hours or less after stroke onset, and even transient ischemia can induce marked extravasation (Nishimura et al, 2006 ; Zhang and Murphy, 2007 ; Zhu et al, 2017b ). The restoration of the disrupted BBB takes hours or even days depending on the duration and severity of stroke.…”

“…The restoration of the disrupted BBB takes hours or even days depending on the duration and severity of stroke. The disrupted BBB induced by transient ischemia can be restored within hours (Zhu et al, 2017b ), but the prolonged increase in vascular permeability can still be detected from day 3 to day 21 after middle cerebral artery occlusion (MCAO; Lin et al, 2008 ).…”

Fasudil alleviates brain damage in rats after carbon monoxide poisoning through regulating neurite outgrowth inhibitor/oligodendrocytemyelin glycoprotein signalling pathway

“…Many diseases and pathological conditions, such as depression, Alzheimer's disease, cerebral ischaemia, CO poisoning and sleep deprivation, can damage the integrity of hippocampal ultrastructure, which is closely related to the synaptic plasticity and the decline in learning and memory function. Synaptic plasticity plays a very important role in this process . By a mouse model with synapsin caveolin‐1(SynCav1) administration, the Egawa study demonstrated that SynCav1 augmented synaptic plasticity by increasing total number of synapses, presynaptic vesicles (PSVs) per bouton, splitting synapse boutons and myelination, all of which were gross anatomical and microscopic indicators of structural neuroplasticity.…”

“…Synaptic plasticity plays a very important role in this process. 26 By a mouse model with synapsin caveolin-1(SynCav1) administration, the Egawa study demonstrated that SynCav1 augmented synaptic plasticity by increasing total number of synapses, presynaptic vesicles (PSVs) per bouton, splitting synapse boutons and myelination, all of which were gross anatomical and microscopic indicators of structural neuroplasticity. Combined with the measurable electrophysiological changes, these ultrastructural alterations in hippocampus improved learning and memory, suggesting that caveolin-1 (Cav-1) may be an attractive molecular target to repair brain function in the context of neurodegenerative diseases.…”