The activation of α2-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

Kim, Sung‐Su; Park, Soo-Hyun; Lee, Jae Ryeong; Jung, Jun‐Sub; Suh, Hwal

doi:10.4196/kjpp.2017.21.5.495

Cited by 4 publications

(3 citation statements)

References 58 publications

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“…In a rat model of ischemia, researchers observed that Dex mitigated inflammation through inactivating the TLR-4/NF-κB pathway [35]. In another study, pretreatment with clonidine attenuated the sepsis-induced plasma TNF-α level [36]. Similarly, we also observed that brimonidine effectively inhibited the increased expression of NF-κB, TNF-α, and IL-6 in the facial motor neurons.…”

Section: Discussionsupporting

confidence: 65%

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation

Cai

Song

et al. 2021

ORL

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Objective: This study aimed to investigate the potential neuroprotective action of brimonidine against facial nerve crush injury in rats and the possible underlying mechanisms. Methods: Sixty Wistar adult rats were randomly and equally divided into 3 groups: 40 rats underwent unilateral facial nerve crush injury and were administered with either saline (intraperitoneal, n = 20) or brimonidine 1 mg/kg/day (intraperitoneal, n = 20) for 5 consecutive days. Functional and electromyographic recovery was recorded postoperatively. The facial nucleus of 5 mice in each group was analyzed for mRNA expression levels of GFAP, PAF, NT-4, P75NTR, NF-κB, TNF-α, IL-6, and α2-ARs by qRT-PCR. Results: Brimonidine promoted the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining and electron microscopy showed significant recovery of Schwann cells and axons in the brimonidine group. Brimonidine attenuated the crush-induced upregulation in GFAP and PAF mRNA (p < 0.05), as well as enhanced the mRNA levels of NT-4 and P75NTR (p < 0.05), while decreased the expression of NF-κB, TNF-α and IL-6 (p < 0.05). Conclusions: Brimonidine could promote the recovery of facial nerve crush injury in rats via suppressing of GFAP/PAF activation and neuroinflammation and increasing neurotrophic factors. Brimonidine may be apromising candidate agent for the treatment of facial nerve injury.

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Section: Discussionsupporting

confidence: 65%

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation

Cai

Song

et al. 2021

ORL

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“…In mice mortality from sepsis is reduced by the infusion of glucose in a dose dependent manner but only early in the hypo inflammatory phase of sepsis [30,31].…”

Section: Glucosementioning

confidence: 99%

Thiamine and High Dose Insulin Treatment for Sepsis

Bradley¹

2023

Preprint

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Sepsis is a major health problem and accounts for 20 per cent of deaths worldwide. It is the most expensive condition treated in United States hospitals at $27 billion per year or about $20,000 per patient. Treatment consisting largely of fluid resuscitation and antibiotics has only marginal impact. Mortality is about 27 per cent for hospitalized patients and about 42 per cent for patients in intensive care.There are two phases of sepsis – a hyper inflammatory phase and a subsequent hypo inflammatory phase.During the hyper inflammatory phase the metabolic rate increases associated with an increase in body temperature and a rapid escalation of immune system functioning including increased numbers of leucocytes and migration of those leucocytes to infected and damaged tissues and an increased supply and consumption of glucose to fuel this immune system.During the subsequent hypo inflammatory phase the metabolic rate declines and this is associated with a decrease in body temperature and a generalized decrease in the physiological activity of many organs including the immune system akin to hibernation. The activated immune system has priority for the available glucose over most other organs and physiological functions during such potentially life threatening circumstances. Thus adenosine triphosphate (ATP) production by mitochondria (the source of energy at the cellular level for the organism as a whole) also has a lower priority for the available glucose relative to the activated immune system. If glucose availability is threatened then mitochondrial production of ATP is partially or substantially suppressed in favor of glycolysis because glycolysis can rapidly produce large quantities of ATP that are necessary for immune cell function in infected, anaerobic, ischemic, or damaged tissues.However, glycolysis is only a temporary fix as it cannot produce the quantities of ATP necessary on an ongoing basis for the normal functioning of the healthy animal. Mitochondrial production of ATP must be recommenced for full recovery.It appears that the partial or substantial suppression of mitochondrial production of ATP by activation of the immune response becomes relatively fixated in some patients leading to a substantial ATP deficit. This is the fundamental issue of sepsis.This paper reviews the metabolism of glucose and insulin during sepsis and concludes that high dose insulin with mild hyper glycaemia in conjunction with the intravenous administration of thiamine, an inhibitor of the pyruvate dehydrogenase kinase enzymes, to re-establish physiological ATP production by mitochondria, administered early in the hypo metabolic (hypo inflammatory) phase of sepsis should significantly improve survival.

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“…In mice, mortality from sepsis is reduced by the infusion of glucose in a dose-dependent manner but only early in the hypoinflammatory phase of sepsis [30,31].…”

Section: Glucosementioning

confidence: 99%

Thiamine and High Dose Insulin Treatment for Sepsis

Bradley

2023

CAJMHE

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Sepsis is a major health problem and accounts for 20% of deaths worldwide. It is the most expensive condition treated in United States hospitals at $62 billion per year or about $46,000 per patient. Treatment consisting largely of fluid resuscitation and antibiotics has only a marginal impact. Mortality is about 27% for hospitalised patients and about 42% for patients in intensive care. There are two phases of sepsis – a hyperinflammatory phase and a subsequent hypoinflammatory phase. During the hyperinflammatory phase, the metabolic rate increases, and this is associated with an increase in body temperature and a rapid escalation of immune system functioning including increased numbers of leucocytes and their migration to infected and damaged tissues and increased supply and consumption of glucose to fuel this immune system. During the subsequent hypoinflammatory phase, the metabolic rate decreases, and this is associated with a decrease in body temperature and a generalised decrease in the physiological activity of many organs including the immune system akin to hibernation. The activated immune system has priority for the available glucose over most other organs and physiological functions during such potentially life-threatening circumstances. Thus, adenosine triphosphate (ATP) production by mitochondria (the source of energy at the cellular level for the organism as a whole) also has a lower priority for the available glucose relative to the activated immune system. If glucose availability is threatened, then the mitochondrial production of ATP is partially or substantially suppressed in favour of glycolysis because glycolysis can rapidly produce large quantities of ATP that are necessary for immune cell function in infected, anaerobic, ischaemic, or damaged tissues. However, glycolysis is only a temporary fix as it cannot produce the quantities of ATP necessary on an ongoing basis for the normal functioning of the healthy animal. Mitochondrial production of ATP must be recommenced for full recovery. It appears that the partial or substantial suppression of mitochondrial production of ATP by activation of the immune response becomes relatively fixated in some patients, leading to a substantial ATP deficit. This is the fundamental issue of sepsis. This paper reviews the metabolism of glucose and insulin during sepsis and concludes that high dose insulin with mild hyperglycaemia in conjunction with the intravenous administration of thiamine, an inhibitor of the pyruvate dehydrogenase kinase enzymes, to re-establish physiological ATP production by mitochondria, administered early in the hypometabolic (hypoinflammatory) phase of sepsis, may enhance survival relative to thiamine alone.

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The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

Cited by 4 publications

References 58 publications

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation

<strong></strong>Thiamine and High Dose Insulin Treatment for Sepsis<strong> </strong>

Thiamine and High Dose Insulin Treatment for Sepsis

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