Continuous Monitoring of Spreading Depolarization and Cerebrovascular Autoregulation after Aneurysmal Subarachnoid Hemorrhage

Sugimoto, Kazutaka; Shirao, Satoshi; Koizumi, Hiroyasu; Inoue, Takao; Oka, Fumiaki; Maruta, Yuichi; Suehiro, Eiichi; Sadahiro, Hirokazu; Oku, Takayuki; Yanagawa, Hiroshi; Ishihara, Hideyuki; Nomura, Sadahiro; Suzuki, Michiyasu

doi:10.1016/j.jstrokecerebrovasdis.2016.07.007

Cited by 20 publications

(15 citation statements)

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“…This fully reversible neural response propagates very slowly (propagation velocity in the order of few mm/min) from the initially stimulated point to more and more remote parts of the tissue (Lima et al, 2017). CSD has been linked to brain excitability disorders and its diseases such as migraine with aura (Peeters et al, 2007; Vinogradova, 2018), multiple sclerosis (Pusic et al, 2015), epilepsy (Tamaki et al, 2017), traumatic brain injury (Mayevsky et al, 1998; Hartings et al, 2009), subarachnoid hemorrhage (Dreier et al, 2006; Sugimoto et al, 2016), and malignant ischemic stroke (Woitzik et al, 2013; Pinczolits et al, 2017). CSD has been demonstrated not only in experimental animals (Guedes et al, 2017; Accioly and Guedes, 2017) but also in humans (Carlson et al, 2016; Lauritzen and Strong, 2016).…”

Section: Introductionmentioning

confidence: 99%

Sub-Convulsing Dose Administration of Pilocarpine Reduces Glycemia, Increases Anxiety-Like Behavior and Decelerates Cortical Spreading Depression in Rats Suckled on Various Litter Sizes

Francisco

Guedes

2018

Front. Neurosci.

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Epilepsy and malnutrition constitute two worldwide health problems affecting behavior and brain function. The cholinergic agonist pilocarpine (300–380 mg/kg; single administration) reproduces the human type of temporal lobe epilepsy in rats. Pilocarpine-induced epilepsy in rodents has been associated with glycemia, learning and memory and anxiety disturbances. Cortical spreading depression (CSD) is a neural response that has been linked to brain excitability disorders and its diseases, and has been shown to be antagonized by acute pilocarpine. This study aimed to further investigate the effect of chronic pilocarpine at a sub-convulsing dose on weight gain, blood glucose levels, anxiety-like behavior and CSD. In addition, we tested whether unfavorable lactation-induced malnutrition could modulate the pilocarpine effects. Wistar rats were suckled under normal size and large size litters (litters with 9 and 15 pups; groups L9 and L15, respectively). From postnatal days (PND) 35–55, these young animals received a daily intraperitoneal injection of pilocarpine (45 mg/kg/day), or vehicle (saline), or no treatment (naïve). On PND58, the animals were behaviorally tested in an open field apparatus. This was immediately followed by 6 h fasting and blood glucose measurement. At PND60–65, CSD was recorded, and its parameters (velocity of propagation, amplitude, and duration) were calculated. Compared to the control groups, pilocarpine-treated animals presented with reduced weight gain and lower glycemia, increased anxiety-like behavior and decelerated CSD propagation. CSD velocity was higher (p < 0.001) in the L15 groups in comparison to the corresponding groups in the L9 condition. The results demonstrate an influence of chronic (21-day) administration of a sub-convulsing, very low dose (45 mg/kg) of pilocarpine on CSD propagation, anxiety-like behavior, glycemia and body weight. Furthermore, data reinforce the hypothesis of a relationship between CSD and brain excitability. The lactation condition seems to differentially modulate these effects.

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Section: Introductionmentioning

confidence: 99%

Sub-Convulsing Dose Administration of Pilocarpine Reduces Glycemia, Increases Anxiety-Like Behavior and Decelerates Cortical Spreading Depression in Rats Suckled on Various Litter Sizes

Francisco

Guedes

2018

Front. Neurosci.

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“…Cerebrovascular smooth muscle cells constrict in response to the massive accumulation of K + more than 20 mM in the extravascular or perivascular space with SD, aggravated by the restricted availability of nitric oxide [ 16 , 19 , 20 ]. Further, clinical studies have demonstrated that spreading ischemia may coincide with the dysfunction of cerebrovascular autoregulation after traumatic brain injury or subarachnoid hemorrhage [ 21 , 22 ]. Also, an experimental study linked SD-related spreading ischemia to autoregulatory failure in the context of hypovolemic hypotension [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Intriguingly, spreading ischemia coupled with SD was found to be coincident with the loss of cerebral autoregulation in patients with traumatic brain injury and a case of subarachnoid hemorrhage [ 21 , 22 ]. Intuitively, spreading ischemia may be concurrent with autoregulatory failure in ischemic stroke as well, but this has not been demonstrated yet.…”

Section: Introductionmentioning

confidence: 99%

Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex

et al. 2021

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Background In ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response. Methods Incomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20–40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4–5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K+ concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis. Results Ischemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K+ concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx < 0.3). In contrast, aSD was superimposed on autoregulatory failure (rCBFx > 0.3) because CBF followed the decreasing MABP. CBF dropped 15–20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD. Conclusions We propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling.

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“…For example, the study on duration of SDs discussed above also found that the longer the SD, the more likely it was that the SD would cause reduced blood flow and DCI [22]. A case report building on these findings used a continuous measure of cerebral autoregulation and found an association between impaired cerebrovascular regulation and increased duration of SD-related depressions [31].…”

Section: Potential Sd-mediated Causes Of Injurymentioning

confidence: 96%

Spreading Depolarizations and Subarachnoid Hemorrhage

Sugimoto

Chung

2020

Neurotherapeutics

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Cortical spreading depolarizations (SD) are strongly associated with worse tissue injury and clinical outcomes in the setting of aneurysmal subarachnoid hemorrhage (SAH). Animal studies have suggested a causal relationship, and new therapies to target SDs are starting to be tested in clinical studies. A recent set of single-center randomized trials assessed the effect of the phosphodiesterase inhibitor cilostazol in patients with SAH. Cilostazol led to improved functional outcomes and SD-related metrics in treated patients through a putative mechanism of improved cerebral blood flow. Another promising therapeutic approach includes attempts to block SDs with, for example, the NMDA receptor antagonist ketamine. SDs have emerged not only as a therapeutic target but also as a potentially useful biomarker for brain injury following SAH. Additional clinical and preclinical experimental work is greatly needed to assess the generalizability of existing therapeutic trials and to better delineate the relationship between SDs, SAH, and functional outcome.

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Continuous Monitoring of Spreading Depolarization and Cerebrovascular Autoregulation after Aneurysmal Subarachnoid Hemorrhage

Cited by 20 publications

References 29 publications

Sub-Convulsing Dose Administration of Pilocarpine Reduces Glycemia, Increases Anxiety-Like Behavior and Decelerates Cortical Spreading Depression in Rats Suckled on Various Litter Sizes

Sub-Convulsing Dose Administration of Pilocarpine Reduces Glycemia, Increases Anxiety-Like Behavior and Decelerates Cortical Spreading Depression in Rats Suckled on Various Litter Sizes

Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex

Spreading Depolarizations and Subarachnoid Hemorrhage

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