Abstract
Anoxic depolarization (AD) is a hallmark of ischemic brain damage. AD is associated with a spreading wave of neuronal depolarization and an increase in light transmittance. However, initiation and spread of AD across the layers of the somatosensory cortex, which is one of the most frequently affected brain regions in ischemic stroke, remains largely unknown. Here, we explored the initiation and propagation of AD in slices of the rat barrel cortex using extracellular local field potential (LFP) recordings and optical intrinsic signal (OIS) recordings. We found that ischemia-like conditions induced by oxygen-glucose deprivation (OGD) evoked AD, which manifested as a large negative LFP shift and an increase in light transmittance. AD typically initiated in one or more barrels and further spread across the entire slice with a preferential propagation through L4. Elevated extracellular potassium concentration accelerated the AD onset without affecting proneness of L4 to AD. In live slices, barrels were most heavily labeled by the metabolic level marker 2,3,5-triphenyltetrazolium chloride, suggesting that the highest metabolic demand is in L4 when compared to the other layers. Thus, L4 is the layer of the barrel cortex most prone to AD, which may be due to the highest metabolic demand and cell density in this layer.
Highlights
The brain is highly metabolically active and vulnerable to metabolic insults
We explored spatial-temporal dynamics of the oxygen-glucose deprivation (OGD)-induced Anoxic depolarization (AD) in slices of the barrel cortex using extracellular recordings of local field potential (LFP), and optical intrinsic signal (OIS) recordings (Figures 1A,B)
The principal conclusion emerging from the present study is that different layers of the barrel cortex differ in their propensity to AD and that L4 is the most prone to AD
Summary
The brain is highly metabolically active and vulnerable to metabolic insults. During global or focal ischemia, the limited supply of oxygen and glucose causes a fall in ATP levels, arrest in sodium-potassium pump activity and depolarization of neurons in the metabolically deprived brain regions (Lipton, 1999; Somjen, 2001). Release of potassium and glutamate into the extracellular space accelerates depolarization of the adjacent neurons igniting an avalanchelike wave of collective Anoxic Depolarization (AD), which shares many common features with the spreading depression (SD) described by Leao (Leao, 1947; Nedergaard and Hansen, 1993; Somjen, 2001; Pietrobon and Moskowitz, 2014; Dreier and Reiffurth, 2015; Hartings et al, 2017). Factors that increase metabolic activity such as increased neuronal activity or elevated temperature accelerate AD onset and ischemic neuronal death, whereas reduction in metabolic demand is neuroprotective against ischemic damage (Dzhala et al, 2000; Joshi and Andrew, 2001; Tyzio et al, 2006)
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