Anoxia and Neural Metabolism

Mechanisms underlying pathological cortical bursts during metabolic depletion

“…Although we are not aware of experiments that have investigated changes in neural activity across multiple controlled values of [K + ] Buffer and [O 2 ] Buffer , independent evidence supports the emergence of seizure-like activity for higher [K + ] Buffer 59 , 60 , and conversely, for lower [O 2 ] Buffer 22 . Moreover, substantial evidence suggests that hypoxia increases extracellular potassium 9 , 30 – 42 , 61 – 66 , thus supporting our fundamental approach that understanding the response to hypoxia activity requires a joint modeling of both [K + ] Buffer and [O 2 ] Buffer . More broadly, we suggest that systematically mapping out the [K + ] Buffer -[O 2 ] Buffer plane in experimental systems could prove fruitful in understanding dynamics under metabolically challenged conditions and provide independent validation of our model.…”

“…Our exploration of recovery trajectories revealed that in addition to timely reoxygenation, an increase in [K + ] Buffer facilitates the restoration of healthy dynamics by preventing the over-correction of [K + ] o during re-oxygenation. This suggests that a substantial increase in potassium following hypoxia (as observed empirically 30 – 41 , 50 ) could be a protective mechanism that brings the dynamics closer to the BS regime. In the BS regime, the estimated parameter trajectories inferred from EEG data suggest effective potassium clearance during reoxygenation for babies with good recovery, and its failure for babies with poor recovery.…”

“…A hypoxic insult was introduced by decreasing [O 2 ] Buffer from its normal value of 32 mg/L to values where the network enters the isoelectric state. Because extracellular K + is known to increase in the brain post hypoxic insults 30 – 42 , we also explored the effect of increased [K + ] Buffer during the post hypoxic recovery.…”

“…The parameter [K + ] Buffer is an effective value describing the collective buffering capacity of various sources of potassium, particularly crucial during metabolically challenged states. For example, during hypoxic insult, a decrease in potassium concentration of the tissue and its simultaneous increase in surrounding areas have been observed in vitro 30 – 34 and in vivo 35 – 37 . Hypoxia also induces a five-to-ten-fold increase in potassium concentration more distally in the subarachnoid fluid 38 , 39 , with moderate increases in the blood plasma 38 , 40 , cisterna magna fluid 38 , 40 , cortical cerebrospinal fluid 41 , and on the cortical surface 42 .…”

Mechanisms underlying pathological cortical bursts during metabolic depletion

“…Although we are not aware of experiments that have investigated changes in neural activity across multiple controlled values of [K + ] Buffer and [O 2 ] Buffer , independent evidence supports the emergence of seizure-like activity for higher [K + ] Buffer 59 , 60 , and conversely, for lower [O 2 ] Buffer 22 . Moreover, substantial evidence suggests that hypoxia increases extracellular potassium 9 , 30 – 42 , 61 – 66 , thus supporting our fundamental approach that understanding the response to hypoxia activity requires a joint modeling of both [K + ] Buffer and [O 2 ] Buffer . More broadly, we suggest that systematically mapping out the [K + ] Buffer -[O 2 ] Buffer plane in experimental systems could prove fruitful in understanding dynamics under metabolically challenged conditions and provide independent validation of our model.…”

“…Our exploration of recovery trajectories revealed that in addition to timely reoxygenation, an increase in [K + ] Buffer facilitates the restoration of healthy dynamics by preventing the over-correction of [K + ] o during re-oxygenation. This suggests that a substantial increase in potassium following hypoxia (as observed empirically 30 – 41 , 50 ) could be a protective mechanism that brings the dynamics closer to the BS regime. In the BS regime, the estimated parameter trajectories inferred from EEG data suggest effective potassium clearance during reoxygenation for babies with good recovery, and its failure for babies with poor recovery.…”

“…A hypoxic insult was introduced by decreasing [O 2 ] Buffer from its normal value of 32 mg/L to values where the network enters the isoelectric state. Because extracellular K + is known to increase in the brain post hypoxic insults 30 – 42 , we also explored the effect of increased [K + ] Buffer during the post hypoxic recovery.…”

“…The parameter [K + ] Buffer is an effective value describing the collective buffering capacity of various sources of potassium, particularly crucial during metabolically challenged states. For example, during hypoxic insult, a decrease in potassium concentration of the tissue and its simultaneous increase in surrounding areas have been observed in vitro 30 – 34 and in vivo 35 – 37 . Hypoxia also induces a five-to-ten-fold increase in potassium concentration more distally in the subarachnoid fluid 38 , 39 , with moderate increases in the blood plasma 38 , 40 , cisterna magna fluid 38 , 40 , cortical cerebrospinal fluid 41 , and on the cortical surface 42 .…”

Action of potassium ions on brain metabolism

“…Such liberated K could cause rapid and profound inhibition of glycolysis in anaerobic regions still supplied with glucose. In regions with full aeration, on the other hand, a rapid increase in glycolysis above normal would be anticipated, which might lead to excessive activity at the periphery of the damaged area (see Gerard, 1938). The anaerobic inhibition of glycolysis by K is probably irreversible.…”

Mechanisms underlying pathological cortical bursts during metabolic depletion

“…Although we are not aware of experiments that have investigated changes in neural activity across multiple controlled values of [K + ] Buffer and [O 2 ] Buffer , independent evidence supports the emergence of seizure-like activity for higher [K + ] Buffer 59 , 60 , and conversely, for lower [O 2 ] Buffer 22 . Moreover, substantial evidence suggests that hypoxia increases extracellular potassium 9 , 30 – 42 , 61 – 66 , thus supporting our fundamental approach that understanding the response to hypoxia activity requires a joint modeling of both [K + ] Buffer and [O 2 ] Buffer . More broadly, we suggest that systematically mapping out the [K + ] Buffer -[O 2 ] Buffer plane in experimental systems could prove fruitful in understanding dynamics under metabolically challenged conditions and provide independent validation of our model.…”

“…Our exploration of recovery trajectories revealed that in addition to timely reoxygenation, an increase in [K + ] Buffer facilitates the restoration of healthy dynamics by preventing the over-correction of [K + ] o during re-oxygenation. This suggests that a substantial increase in potassium following hypoxia (as observed empirically 30 – 41 , 50 ) could be a protective mechanism that brings the dynamics closer to the BS regime. In the BS regime, the estimated parameter trajectories inferred from EEG data suggest effective potassium clearance during reoxygenation for babies with good recovery, and its failure for babies with poor recovery.…”

“…A hypoxic insult was introduced by decreasing [O 2 ] Buffer from its normal value of 32 mg/L to values where the network enters the isoelectric state. Because extracellular K + is known to increase in the brain post hypoxic insults 30 – 42 , we also explored the effect of increased [K + ] Buffer during the post hypoxic recovery.…”

“…The parameter [K + ] Buffer is an effective value describing the collective buffering capacity of various sources of potassium, particularly crucial during metabolically challenged states. For example, during hypoxic insult, a decrease in potassium concentration of the tissue and its simultaneous increase in surrounding areas have been observed in vitro 30 – 34 and in vivo 35 – 37 . Hypoxia also induces a five-to-ten-fold increase in potassium concentration more distally in the subarachnoid fluid 38 , 39 , with moderate increases in the blood plasma 38 , 40 , cisterna magna fluid 38 , 40 , cortical cerebrospinal fluid 41 , and on the cortical surface 42 .…”

Action of potassium ions on brain metabolism

“…Such liberated K could cause rapid and profound inhibition of glycolysis in anaerobic regions still supplied with glucose. In regions with full aeration, on the other hand, a rapid increase in glycolysis above normal would be anticipated, which might lead to excessive activity at the periphery of the damaged area (see Gerard, 1938). The anaerobic inhibition of glycolysis by K is probably irreversible.…”

Mechanisms underlying pathological cortical bursts during metabolic depletion

“…Although we are not aware of experiments that have investigated changes in neural activity across multiple controlled values of [K + ] Buffer and [O 2 ] Buffer , independent evidence supports the emergence of seizure-like activity for higher [K + ] Buffer 59 , 60 , and conversely, for lower [O 2 ] Buffer 22 . Moreover, substantial evidence suggests that hypoxia increases extracellular potassium 9 , 30 – 42 , 61 – 66 , thus supporting our fundamental approach that understanding the response to hypoxia activity requires a joint modeling of both [K + ] Buffer and [O 2 ] Buffer . More broadly, we suggest that systematically mapping out the [K + ] Buffer -[O 2 ] Buffer plane in experimental systems could prove fruitful in understanding dynamics under metabolically challenged conditions and provide independent validation of our model.…”

“…Our exploration of recovery trajectories revealed that in addition to timely reoxygenation, an increase in [K + ] Buffer facilitates the restoration of healthy dynamics by preventing the over-correction of [K + ] o during re-oxygenation. This suggests that a substantial increase in potassium following hypoxia (as observed empirically 30 – 41 , 50 ) could be a protective mechanism that brings the dynamics closer to the BS regime. In the BS regime, the estimated parameter trajectories inferred from EEG data suggest effective potassium clearance during reoxygenation for babies with good recovery, and its failure for babies with poor recovery.…”

“…A hypoxic insult was introduced by decreasing [O 2 ] Buffer from its normal value of 32 mg/L to values where the network enters the isoelectric state. Because extracellular K + is known to increase in the brain post hypoxic insults 30 – 42 , we also explored the effect of increased [K + ] Buffer during the post hypoxic recovery.…”

“…The parameter [K + ] Buffer is an effective value describing the collective buffering capacity of various sources of potassium, particularly crucial during metabolically challenged states. For example, during hypoxic insult, a decrease in potassium concentration of the tissue and its simultaneous increase in surrounding areas have been observed in vitro 30 – 34 and in vivo 35 – 37 . Hypoxia also induces a five-to-ten-fold increase in potassium concentration more distally in the subarachnoid fluid 38 , 39 , with moderate increases in the blood plasma 38 , 40 , cisterna magna fluid 38 , 40 , cortical cerebrospinal fluid 41 , and on the cortical surface 42 .…”

Action of potassium ions on brain metabolism

“…Such liberated K could cause rapid and profound inhibition of glycolysis in anaerobic regions still supplied with glucose. In regions with full aeration, on the other hand, a rapid increase in glycolysis above normal would be anticipated, which might lead to excessive activity at the periphery of the damaged area (see Gerard, 1938). The anaerobic inhibition of glycolysis by K is probably irreversible.…”