Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

Wilson, Robert H.; Crouzet, Christian; Lee, Donald E.; Donga, Dishant; Patel, Ayushi; Bazrafkan, Afsheen; Maki, Niki; Rafi, Masih A.; Moslehyazdi, Maziar; Pham, Justin H.; Torabzadeh, Mohammad; Hjelm, Brooke E.; Tromberg, Bruce J.; Steward, Oswald; Lopour, Beth A.; Choi, Bernard; Akbari, Yama

doi:10.1101/786210

Cited by 5 publications

(13 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, with the prevalence of cardiac arrest and occlusive stroke because of increased life span coupled with unhealthy lifestyles, SD in response to restricted blood flow in patients likely becomes deleterious rather than advantageous. Nevertheless, in a preclinical rodent model of global cerebral ischemia, earlier SD onset is predictive of improved neurological outcome (Wilson et al 2019). There is also increasing willingness to consider that, under some circumstances, SD in mammalian brains could be beneficial by preconditioning tissue and/or limiting the expansion of damage (Shuttleworth et al 2020).…”

Section: Adaptive Valuementioning

confidence: 99%

Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Robertson

Dawson‐Scully

Andrew

2020

Journal of Neurophysiology

View full text Add to dashboard Cite

Neural function depends on maintaining cellular membrane potentials as the basis for electrical signaling. Yet, in mammals and insects, neuronal and glial membrane potentials can reversibly depolarize to zero, shutting down neural function by the process of spreading depolarization (SD) that collapses the ion gradients across membranes. SD is not evident in all metazoan taxa with centralized nervous systems. We consider the occurrence and similarities of SD in different animals and suggest that it is an emergent property of nervous systems that have evolved to control complex behaviors requiring energetically expensive, rapid information processing in a tightly regulated extracellular environment. Whether SD is beneficial or not in mammals remains an open question. However, in insects, it is associated with the response to harsh environments and may provide an energetic advantage that improves the chances of survival. The remarkable similarity of SD in diverse taxa supports a model systems approach to understanding the mechanistic underpinning of human neuropathology associated with migraine, stroke, and traumatic brain injury.

show abstract

Section: Adaptive Valuementioning

confidence: 99%

Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Robertson

Dawson‐Scully

Andrew

2020

Journal of Neurophysiology

View full text Add to dashboard Cite

show abstract

“…In contrast, anoxic SD, a type of SD caused by anoxia or asphyxia, is persistent until return of blood flow or oxygen, after which repolarization may occur [1]. Anoxic SD is also seen in global ischemia produced by cardiac arrest and has been recently found by our laboratory to be related to outcome [9]. Specifically, in that study, an earlier anoxic SD during cardiac arrest was correlated with better outcome post resuscitation [9,10].…”

Section: Introductionmentioning

confidence: 60%

Cortical Anoxic Spreading Depolarization During Cardiac Arrest is Associated with Remote Effects on Peripheral Blood Pressure and Postresuscitation Neurological Outcome

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Spreading depolarizations (SDs) are self-propagating waves of neuronal and glial depolarizations often seen in neurological conditions in both humans and animal models. Because SD is thought to worsen neurological injury, the role of SD in a variety of cerebral insults has garnered significant investigation. Anoxic SD is a type of SD that occurs because of anoxia or asphyxia. Although asphyxia leading to a severe drop in blood pressure may affect cerebral hemodynamics and is widely known to cause anoxic SD, the effect of anoxic SD on peripheral blood pressure in the extremities has not been investigated. This relationship is especially important to understand for conditions such as circulatory shock and cardiac arrest that directly affect both peripheral and cerebral perfusion in addition to producing anoxic SD in the brain. Methods In this study, we used a rat model of asphyxial cardiac arrest to investigate the role of anoxic SD on cerebral hemodynamics and metabolism, peripheral blood pressure, and the relationship between these variables in 8- to 12-week-old male rats. We incorporated a multimodal monitoring platform measuring cortical direct current simultaneously with optical imaging. Results We found that during anoxic SD, there is decoupling of peripheral blood pressure from cerebral blood flow and metabolism. We also observed that anoxic SD may modify cerebrovascular resistance. Furthermore, shorter time difference between anoxic SDs measured at different locations in the same rat was associated with better neurological outcome on the basis of the recovery of electrocorticography activity (bursting) immediately post resuscitation and the neurological deficit scale score 24 h post resuscitation. Conclusions To our knowledge, this is the first study to quantify the relationship between peripheral blood pressure, cerebral hemodynamics and metabolism, and neurological outcome in anoxic SD. These results indicate that the characteristics of SD may not be limited to cerebral hemodynamics and metabolism but rather may also encompass changes in peripheral blood flow, possibly through a brain–heart connection, providing new insights into the role of anoxic SD in global ischemia and recovery.

show abstract

“…Neurological recovery in surviving rats was quantified using the Neurological Deficit Scale (NDS; Table 1 ). The NDS consists of components that measure arousal, brainstem function, motor and sensory activities, as described previously ( Kang et al, 2017 ; Wilson et al, 2019 ). Neurological recovery was evaluated at 4, 24, 48, and 72 h post-CA by well-trained personnel who were blind to dietary groupings.…”

Section: Methodsmentioning

confidence: 99%

Overnight Caloric Restriction Prior to Cardiac Arrest and Resuscitation Leads to Improved Survival and Neurological Outcome in a Rodent Model

et al. 2021

Self Cite

View full text Add to dashboard Cite

While interest toward caloric restriction (CR) in various models of brain injury has increased in recent decades, studies have predominantly focused on the benefits of chronic or intermittent CR. The effects of ultra-short, including overnight, CR on acute ischemic brain injury are not well studied. Here, we show that overnight caloric restriction (75% over 14 h) prior to asphyxial cardiac arrest and resuscitation (CA) improves survival and neurological recovery as measured by, behavioral testing on neurological deficit scores, faster recovery of quantitative electroencephalography (EEG) burst suppression ratio, and complete prevention of neurodegeneration in multiple regions of the brain. We also show that overnight CR normalizes stress-induced hyperglycemia, while significantly decreasing insulin and glucagon production and increasing corticosterone and ketone body production. The benefits seen with ultra-short CR appear independent of Sirtuin 1 (SIRT-1) and brain-derived neurotrophic factor (BDNF) expression, which have been strongly linked to neuroprotective benefits seen in chronic CR. Mechanisms underlying neuroprotective effects remain to be defined, and may reveal targets for providing protection pre-CA or therapeutic interventions post-CA. These findings are also of high importance to basic sciences research as we demonstrate that minor, often-overlooked alterations to pre-experimental dietary procedures can significantly affect results, and by extension, research homogeneity and reproducibility, especially in acute ischemic brain injury models.

show abstract

Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

Cited by 5 publications

References 94 publications

Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Neural shutdown under stress: an evolutionary perspective on spreading depolarization

Cortical Anoxic Spreading Depolarization During Cardiac Arrest is Associated with Remote Effects on Peripheral Blood Pressure and Postresuscitation Neurological Outcome

Overnight Caloric Restriction Prior to Cardiac Arrest and Resuscitation Leads to Improved Survival and Neurological Outcome in a Rodent Model

Contact Info

Product

Resources

About