Spreading depolarizations occur in human ischemic stroke with high incidence

Dohmen, Christian; Sakowitz, Oliver W.; Fabricius, Martin; Bosche, Bert; Reithmeier, Thomas; Ernestus, Ralf‐Ingo; Brinker, Gerrit; Dreier, Jens P.; Woitzik, Johannes; Strong, Anthony J.; Graf, Rudolf

doi:10.1002/ana.21390

Cited by 384 publications

(390 citation statements)

References 41 publications

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“…We found that inhibition of AMPK using compound-C suppressed SD in 70% of preparations. (Rodgers et al, 2010) that ouabaininduced repetitive SD in the locust resembles peri-infarct depolarizations that prevent the restoration of energy and increase the size of the cortical infarct (Fabricius et al, 2006;Dohmen et al, 2008;Dreier et al, 2009). Given the similarity between locust and mammalian SD phenomena, the modulatory effects of AMPK in our study are highly relevant for understanding the pathology of stroke and seizures.…”

Section: Discussionmentioning

confidence: 84%

Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Rodgers-Garlick

Armstrong²,

Robertson³

2011

J. Neurosci.

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Neural circuits are especially vulnerable to metabolic stress. The locust (Locusta migratoria) responds to anoxia by entering a coma during which neural and muscular systems shut down. During anoxic coma, arrest of the ventilatory central pattern generator is tightly correlated with an abrupt spreading depression (SD)-like increase in extracellular potassium concentration within the metathoracic neuropile. We examined the role of the AMP-activated protein kinase (AMPK), an evolutionarily conserved sensor of cellular energy status, in anoxia-induced ventilatory arrest and SD-like events in the locust. Perfusion of sodium azide (NaN 3 ; mitochondrial toxin) induced SD, temporary coma, and profound changes in the ventilatory motor pattern characterized as a rapid rhythm before coma and a slower rhythm following recovery. AMPK activation using 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimicked the motor pattern changes induced by NaN 3 but did not induce SD and coma. The effects of NaN 3 on the ventilatory rhythm were reversed by perfusion of compound-C (AMPK inhibitor) or glucose, and the effects of AICAR were also reversed by compound-C, confirming the modulatory roles of AMPK and energy status. Ouabain-induced recurring SD was suppressed by inhibition of AMPK and exacerbated by its activation. We show that the motor pattern changes induced by metabolic stress are not the result of SD alone, but that AMPK is necessary and sufficient for these changes and that AMPK activity strongly influences susceptibility to SD.

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Section: Discussionmentioning

confidence: 84%

Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Rodgers-Garlick

Armstrong²,

Robertson³

2011

J. Neurosci.

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“…In the case of experimental models, there is new evidence from serial laser speckle flowmetry suggesting that a single depolarization event can propagate for multiple cycles around the periphery of a small cortical lesion (Supplementary video material), giving rise to observation of recurrent, periodic events at a given locus near the edge of the lesion. The possibility arises that similar behaviour might explain periodicity of depolarizations in the injured human brain (Dohmen et al, 2008). This has important implications: studies comparing patient outcome with brain microdialysate glucose levels have suggested that periods of low/zero glucose level are linked to poor outcome (Vespa et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Persisting Depletion of Brain Glucose following Cortical Spreading Depression, despite Apparent Hyperaemia: Evidence for Risk of an Adverse Effect of Leão's Spreading Depression

Hashemi

Bhatia

Nakamura

et al. 2008

J Cereb Blood Flow Metab

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Rapid sampling microdialysis (rsMD) directed towards the cerebral cortex has allowed identification of a combined time-series signature for glucose and lactate that characterizes peri-infarct depolarization in experimental focal ischaemia, but no comparable data exist for 'classical' cortical spreading depression (CSD) associated with hyperaemia in the normally perfused brain. Here, we examined the rsMD responses of dialysate glucose and lactate to five hyperaemic spreading depressions induced with intracortical microinjections, typically of 1 mol/L KCl, in open-skull preparations in five cats under chloralose anaesthesia. Depolarization was verified with microelectrodes, and laser speckle flowmetry was used to examine propagation of the events and perfusion responses near the MD probe. Ten minutes after depolarization, dialysate glucose fell and lactate rose by 28% and 58% respectively. There was no recovery of dialysate glucose 30 mins after depolarization. Mean baseline indicative cerebral blood flow was 25.5±4.1 mL/100 g/min and mean maximum hyperaemic increase was by 29.6 ± 6 mL/100 g/min; hyperaemia remained present 30 mins after CSD. As CSD events are repetitive, frequent, and often clustered temporally in human acute brain injury, these results indicate a high risk of depletion of extracellular glucose in association with depolarization events of a pattern previously thought to be largely benign.

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“…Four centers of the COSBID group conducted a first study in 16 'malignant' stroke patients (Dohmen et al, 2008). In this study, polyphasic slow potential changes of the ECoG (corresponding to the negative slow voltage variation described by Leao (1947) and by Hartings et al (2006) and simultaneous transient ECoG suppressions were recorded as signatures of CSD; slow potential changes in the absence of ECoG background activity were recorded as signatures of PID .…”

Section: Malignant Hemispheric Strokementioning

confidence: 99%

“…An entirely different scenario may apply in the human brain acutely injured for example by ischemic stroke, brain trauma, or subarachnoid or intracerebral hemorrhage (ICH) (Hansen and Lauritzen, 1984;Strong et al, 2002;Fabricius et al, 2006;Dreier et al, 2006;Dohmen et al, 2008). This has been studied recently in patients who underwent neurosurgery including craniotomy because of their acute brain condition, by using cortical electrode strips similar to the technology applied in epilepsy surgery.…”

Section: Introductionmentioning

confidence: 99%

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

Lauritzen

Dreier

Fabricius

et al. 2010

J Cereb Blood Flow Metab

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668

582

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Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

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Spreading depolarizations occur in human ischemic stroke with high incidence

Cited by 384 publications

References 41 publications

Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Metabolic Stress Modulates Motor Patterning via AMP-Activated Protein Kinase

Persisting Depletion of Brain Glucose following Cortical Spreading Depression, despite Apparent Hyperaemia: Evidence for Risk of an Adverse Effect of Leão's Spreading Depression

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

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