Biology subjects

van Putten, M. J. A. M.

Publications and source records attributed to van Putten, M. J. A. M..

3 recordsLinked to original sources

bioRxiv2023

A neural mass model for the EEG in ischemia

Normal brain function depends on continuous cerebral blood flow for the supply of oxygen and glucose, and is quickly compromised in conditions where the metabolic demand cannot be met. Insufficient cerebral perfusion can result in ischemic stroke, with symptoms ranging from loss of motor or language function to coma, depending on the brain areas affected. Cerebral ischemia also results in changes in the electroencephalogram. Initially, a reduction of the frequency of the rhythms occurs. Depending on the depth and duration of energy deprivation, this eventually leads to the disappearance of all rhythmic activity. Here, we study the relationship between electroencephalogram (EEG) phenomenology and cellular biophysical principles using a model of interacting thalamic and cortical neural masses coupled with energy-dependent synaptic transmission. Our model faithfully reproduces the characteristic EEG phenomenology during acute cerebral ischemia and shows that synaptic arrest occurs before cell swelling and irreversible neuronal depolarization. The early synaptic arrest is attributed to ion homeostatic failure due to dysfunctional Na+/K+-ATPase. Moreover, we show that the excitatory input from relay cells to the cortex controls rhythmic behavior. In particular, weak relay-interneuron interaction manifests in burst-like EEG behavior immediately prior to synaptic arrest. We corroborate our observations with human EEG data from patients undergoing carotid endarterectomy and patients after cardiac arrest with a postanoxic encephalopathy. The model thus reconciles the implications of stroke on a cellular, synaptic and circuit level and provides a basis for exploring other multi-scale therapeutic interventions. Significance statementReliable synaptic transmission and preservation of ion gradients across cellular membranes are essential for physiological brain function and consume significant energy. During cerebral ischemia, synaptic arrest occurs early due to energy deprivation (ED), which is characterized clinically by the loss of physiological electroencephalographic (EEG) rhythms. In this work, we explore connections between cellular and network behavior during ED by means of a novel computational model that describes ion dynamics in the cortex and thalamus, and resulting EEG. We reproduce characteristic EEG behavior during ED and show that synaptic arrest occurs before other pathologies like swelling and depolarization. Moreover, we predict that low excitatory thalamocortical projections cause burst-like EEG patterns before synaptic arrest, which may explain observations regarding post-stroke synaptic reorganization.

neuroscience↗

bioRxiv2022

Preservation of thalamocortical circuitry is essential for good recovery in comatose survivors of cardiac arrest

Continuous EEG monitoring contributes to prediction of neurological outcome in comatose cardiac arrest survivors. While the phenomenology of EEG abnormalities in postanoxic encephalopathy is well-known, the pathophysiology, especially the presumed role of selective synaptic failure is less understood. To further this understanding, we estimate biophysical model parameters from the EEG power spectra from individual patients with a good or poor recovery from a postanoxic encephalopathy. This biophysical model includes intracortical, intrathalamic, and corticothalamic synaptic strengths, as well as synaptic time constants and axonal conduction delays. We used continuous EEG measurements from hundred comatose patients recorded during the first 48 hours post-cardiac arrest, fifty with a poor neurological outcome (Cerebral Performance Category (CPC=5)) and fifty with a good neurological outcome (CPC=1). We only included patients that developed (dis-) continuous EEG activity within 48 hours post-cardiac arrest. For patients with a good outcome, we observed an initial relative excitation in the corticothalamic loop and corticothalamic propagation that subsequently evolved towards values observed in healthy controls. For patients with a poor outcome, we observed an initial increase in the cortical excitation-inhibition ratio, increased relative inhibition in the corticothalamic loop, delayed corticothalamic propagation of neuronal activity, and severely prolonged synaptic time constants, that did not return to physiological values. We conclude that the abnormal EEG evolution in patients with a poor neurological recovery after cardiac arrest may result from persistent and selective synaptic failure that includes corticothalamic circuitry, but also delayed corticothalamic propagation.

neuroscience↗

bioRxiv2021

Ion dynamics at the energy-deprived tripartite synapse

The anatomical and functional organization of neurons and astrocytes at tripartite synapses is essential for reliable neurotransmission, which critically depends on ATP. In low energy conditions, synaptic transmission fails, accompanied by a breakdown of ion gradients, changes in membrane potentials and cell swelling. The resulting cellular damage and cell death are causal to the often devastating consequences of an ischemic stroke. The severity of ischemic damage depends on the age and the brain region in which a stroke occurs, but the reasons for this differential vulnerability are far from understood. In the present study, we address this question by developing a comprehensive biophysical model of a glutamatergic synapse to identify key determinants of synaptic failure during energy deprivation. Our model is based on fundamental biophysical principles, includes dynamics of the most relevant ions, i.e., Na+, K+, Ca2+, Cl- and glutamate, and is calibrated with experimental data. It confirms the critical role of the Na+/K+-ATPase in maintaining ion gradients, membrane potentials and cell volumes. Our simulations demonstrate that the system exhibits two stable states, one physiological and one pathological. During energy deprivation, the physiological state may disappear, forcing a transit to the pathological state, which can be reverted when blocking voltage-gated Na+ and K+ channels. Our model predicts that the transition to the pathological state is favoured if the extracellular space fraction is small. A reduction in the extracellular space volume fraction, as, e.g. observed with ageing, will thus promote the brains susceptibility to ischemic damage. Our work provides new insights into the brains ability to recover from energy deprivation, with translational relevance for diagnosis and treatment of ischemic strokes. Author summaryThe brain consumes energy to keep ion concentrations at normal working conditions. In the case of energy deprivation (ED), e.g., during a stroke, synaptic communication fails first. Inspired by our recent experimental work on ED, we formulated a novel computational model to explore initial events during ED. Our model reproduces time courses for several ions from different experimental data. In some cases, the system returns to baseline upon restoring energy supply. In others, we observe that neurons and astrocytes cannot recover accompanied by cell swelling. There is a threshold depending on the depth and duration of ATP depletion differentiating these cases. Also, smaller extracellular spaces hamper recovery more. This result may explain clinical observations of increased vulnerability to stroke as the size of the extracellular space shrinks with ageing.

biophysics↗