Anoxic depolarization, recovery: effect of brain regions and extracellular space (Hubel et al. 2016)

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Accession:187213
The extent of anoxic depolarization (AD), the initial electrophysiological event during ischemia, determines the degree of brain region-specific neuronal damage. Neurons in higher brain regions have stronger ADs and are more easily injured than neurons in lower brain region. The mechanism leading to such differences is not clear. We use a computational model based on a Hodgkin-Huxley framework which includes neural spiking dynamics, processes of ion accumulation, and homeostatic mechanisms like vascular coupling and Na/K-exchange pumps. We show that a large extracellular space (ECS) explains the recovery failure in high brain regions. A phase-space analysis shows that with a large ECS recovery from AD through potassium regulation is impossible. The code 'time_series.ode' can be used to simulate AD for a large and a small ECS and show the different behaviors. The code ‘continuations.ode’ can be used to show the fixed point structure. Depending on our choice of large or small ECS the fixed point curve implies the presence/absence of a recovery threshold that defines the potassium clearance demand.
Reference:
1 . Hübel N, Andrew RD, Ullah G (2016) Large extracellular space leads to neuronal susceptibility to ischemic injury in a Na+/K+ pumps-dependent manner. J Comput Neurosci 40:177-92 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Abstract single compartment conductance based cell;
Channel(s): I Chloride; I Na,t; I K; I K,leak; I h; I Sodium; I Potassium; I_K,Na; Na/K pump; I Cl, leak; I Na, leak;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: XPP;
Model Concept(s): Action Potentials; Pathophysiology; Sodium pump; Depolarization block; Homeostasis; Potassium buffering;
Implementer(s):
Search NeuronDB for information about:  I Chloride; I Na,t; I K; I K,leak; I h; I Sodium; I Potassium; I_K,Na; Na/K pump; I Cl, leak; I Na, leak;
 
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Huebel_Andrew_Ullah_2015
readme.txt
continuations.ode
time_series.ode
                            
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