Experimental cortical stroke induces aberrant increase of sharp-wave-associated ripples in the hippocampus and disrupts cortico-hippocampal communication

Abstract

The functional consequences of ischemic stroke in the remote brain regions are not well characterized. The current study sought to determine changes in hippocampal oscillatory activity that may underlie the cognitive impairment observed following distal middle cerebral artery occlusion (dMCAO) without causing hippocampal structural damage. Local field potentials were recorded from the dorsal hippocampus and cortex in urethane-anesthetized rats with multichannel silicon probes during dMCAO and reperfusion, or mild ischemia induced by bilateral common carotid artery occlusion (CCAO). Bilateral change of brain state was evidenced by reduced theta/delta amplitude ratio and shortened high theta duration following acute dMCAO but not CCAO. An aberrant increase in the occurrence of sharp-wave-associated ripples (150–250 Hz), crucial for memory consolidation, was only detected after dMCAO reperfusion, coinciding with an increased occurrence of high-frequency discharges (250–450 Hz). dMCAO also significantly affected the modulation of gamma amplitude in the cortex coupled to hippocampal theta phase, although both hippocampal theta and gamma power were temporarily decreased during dMCAO. Our results suggest that MCAO may disrupt the balance between excitatory and inhibitory circuits in the hippocampus and alter the function of cortico-hippocampal network, providing a novel insight in how cortical stroke affects function in remote brain regions.

Pathological changes of brain oscillations following ischemic stroke

“…By recording local field potentials under urethane anesthesia via a linear electrode array spanning the dorsohippocampus to deep cortical layers above, we found that dMCAO acutely altered the brain state in the hippocampus with reduced high-h state and increased low-h state, rendering the LFP with a decreased T/D ratio as compared to the pre stroke recording. 48 This change is similar to the finding in human EEGs near ischemic infarct soon after stroke onset, suggesting that dMCAO affects neural activity in remote brain regions. During MCA occlusion, there was a temporary reduction of h and c power bilaterally in the hippocampus, followed by a gradual recovery towards baseline level.…”

“…The disturbance of signal power in d, h and c persisted after ischemic reperfusion. 48 There was also a significant increase in SPW-R s firing during ischemic reperfusion following MCA occlusion in the CA1 as accompanied by the sharp waves in the stratum radiatum compared to a few ripple events during baseline recording. In addition to SPW-R s, the occurrence of High-Frequency Discharges (HFD) in the range of 250-450 Hz was also increased during ischemic reperfusion following dMCAO (Figure 4), resulting in the increased proportion of HFDs in the pathological range compared to the physiological range of ripples.…”

“…47 Disturbance of physiological ripple oscillation has been reported after experimental stroke during acute and chronic phases. 48,49 Apart from ischemic stroke, changes in SPW-Rs are also observed in murine neurodegenerative disease models. For example, diminished ripple occurrence rates were found in aged mice with human Apolipoprotein E4 knocked in, 50 which led to the loss of hilar GABAergic interneurons, 51 while rTg4510 transgenic mice, a model of tauopathy and dementia, had reduced inhibitory control of the hippocampal network and smaller amplitude-SPW-R. 52 Therefore, a well-orchestrated action between excitation and inhibition is required for the normal physiological function of SPW-R since synchronous activation of excitatory pyramidal cells and certain classes of inhibitory GABAergic interneurons are necessary for SPW-R generation.…”

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

“…The balance of excitatory and inhibitory pathways in the hippocampus is disrupted after middle cerebral artery distal occlusion (MCAO), when the oscillatory activity of the hippocampal EEG curve is more pronounced and the brain connections between the cortex and the hippocampus are disrupted. Impairment is closely related to changes in cognitive function after stroke [ 9 ]. By performing MCAO in the somatosensory cortex and recording the functional dynamics between the cortex and hippocampus, increased cortical activity was found to modulate hippocampal activity [ 10 ].…”

Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage: Involvement of AKT/FoxO3a/ATG‐Mediated Autophagy

“…Oxidative Medicine and Cellular Longevity stroke [28,29]. Other evidence also shows that impaired adult hippocampal neurogenesis is detrimental to the spatial learning and memory after basal ganglia hemorrhage [8].…”