Moderate brain hypothermia started before resuscitation improves survival and neurobehavioral outcomes after CA/CPR in mice

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Recently, ketogenic diet (KD) supplementation has attracted great interest. Therefore, we established the cuprizone (CPZ)-induced demyelination mouse model to investigate the possible neuroprotective effect of KD on the hippocampus of mice. We found that KD significantly elevated the level of serum β-hydroxybutyric acid, improved behavioral and motor abnormalities, and impaired the spatial learning and memory of CPZ-induced demyelination mice. Meanwhile, KD lessened the hippocampal demyelination by enhancing the expression of mature oligodendrocytes (OLs), which was revealed by the elevated expression of MBP and CNPase, as well as the luxol fast blue-staining intensity. Furthermore, KD inhibits the activation of microglia (especially M1-like microglia) and reactive astrocytes. Interestingly, KD attenuated the CPZ-induced oxidative stress by decreasing the malondialdehyde (MDA) content and restoring the glutathione (GSH) levels. In addition, the double immunofluorescence staining revealed that KD enhanced the expression of SIRT1 in astrocytes, microglia, and mature oligodendrocytes. Concomitantly, Western blot demonstrated that KD increased the expression of SIRT1, phosphorylated-AKT, mTOR, and PPAR-γ. In conclusion, KD exerted a neuroprotective effect on CPZ-induced demyelination mice, and this activity was associated with the modulation of the SIRT1/ PPAR-γ and SIRT1/P-Akt/mTOR pathways.

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“…The brain sections were washed in PBS three times, each time for 5 min. Then the sections were stained with H&E for histopathology …”

Section: Experimental Designmentioning

confidence: 99%

“…Then the sections were stained with H&E for histopathology. 33 Nissl Staining. The brain sections were first hydrated in Milli-Q water for 20 min and then placed under agitation in cresyl violet staining solution for 10 min before being rinsed in Milli-Q water.…”

Section: ■ Experimental Designmentioning

confidence: 99%

Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet

Liu

Zhang

et al. 2020

J. Agric. Food Chem.

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“…Some disturbances are given into basic control diagram for the mathematical simulations by Honma et al . [9,12] in this study, to approximate the clinical conditions in selective brain hypothermia [2]. Figure 2 shows the outline of selective brain hypothermia.…”

Section: Methodsmentioning

confidence: 99%

“…Brain hypothermia [1–4] is applied to prevent a brain tissue from further degeneration including secondary damage. In good condition of blood flow, the temperature of the brain tissues is adjusted by blood which circulates and washes out the metabolic fever in the brain.…”

Section: Introductionmentioning

confidence: 99%

Temperature Management Methods for Selective Brain Hypothermia in Variable Metabolism

Honma

Wakamatsu

She

2021

IEEJ Transactions Elec Engng

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Brain hypothermia is widely operated to prevent peripheral healthy brain tissue from secondary damage, caused by increased brain temperature due to hypermetabolism around the damaged areas. Selective brain hypothermia is a new clinical technique of brain hypothermia for a brain disorder. Appropriate solution in a controlled temperature is directly infused into the artery to cool down a brain tissue through some catheters. While the brain temperature is controlled quickly, the body temperature has to be kept within a prescribed range by re‐warmed cerebrovascular blood return to the systemic circulation. As metabolic changes in the brain is variable due to the complex behavior of the disease state with the treatment effect. . In the present study two adaptive control methods as adaptive‐gain control and Fuzzy‐adaptive control are provided to carry out for precise temperature control for selective brain hypothermia. Several kinds of mathematical brain models with cerebrovascular damage are specially used to evaluate our temperature control methods. The effectiveness of the management of the brain temperature is demonstrated for four kinds control laws and five mathematical clinical brain models. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.

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“…41 In a mouse CA model induced by hyperkalemia, TTM (brain temperature 28–32°C) initiation before resuscitation improved survival, reduced hippocampal neuronal injury, and ameliorated spatial memory impairment and anxiety-like behaviors. 42 TTM (33°C) initiated during cardiopulmonary resuscitation (CPR) in a ventricular fibrillation rat CA model achieved better preservation of cerebral microcirculation and reduced apoptosis. 43 However, it should be noted that most of the earlier rodent data are acquired using male animals that are relatively young and healthy, which may limit translation.…”

Section: The Timing Of Ttmmentioning

confidence: 99%

Targeted temperature management and early neuro-prognostication after cardiac arrest

Chen

Lachance

Gao

et al. 2021

J Cereb Blood Flow Metab

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Targeted temperature management (TTM) is a recommended neuroprotective intervention for coma after out-of-hospital cardiac arrest (OHCA). However, controversies exist concerning the proper implementation and overall efficacy of post-CA TTM, particularly related to optimal timing and depth of TTM and cooling methods. A review of the literature finds that optimizing and individualizing TTM remains an open question requiring further clinical investigation. This paper will summarize the preclinical and clinical trial data to-date, current recommendations, and future directions of this therapy, including new cooling methods under investigation. For now, early induction, maintenance for at least 24 hours, and slow rewarming utilizing endovascular methods may be preferred. Moreover, timely and accurate neuro-prognostication is valuable for guiding ethical and cost-effective management of post-CA coma. Current evidence for early neuro-prognostication after TTM suggests that a combination of initial prediction models, biomarkers, neuroimaging, and electrophysiological methods is the optimal strategy in predicting neurological functional outcomes.

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Moderate brain hypothermia started before resuscitation improves survival and neurobehavioral outcomes after CA/CPR in mice

Cited by 5 publications

References 32 publications

Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet

Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet

Temperature Management Methods for Selective Brain Hypothermia in Variable Metabolism

Targeted temperature management and early neuro-prognostication after cardiac arrest

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