Repeated hypoxia exposure induces cognitive dysfunction, brain inflammation, and amyloidβ/p-Tau accumulation through reduced brain O-GlcNAcylation in zebrafish

Repetitive hypoxia (RH) exposure affects the initiation and progression of cognitive dysfunction, but little is known about the mechanisms of hypoxic brain damage. In this study, we show that sublethal RH increased anxiety, impaired learning and memory (L/M), and triggered downregulation of brain levels of glucose and several glucose metabolites in zebrafish, and that supplementation of glucose or glucosamine (GlcN) restored RH-induced L/M impairment. Fear conditioning (FC)-induced brain activation of and PKA/CREB signaling was abrogated by RH, and this effect was reversed by GlcN supplementation. RH was associated with decreased brain O-GlcNAcylation and an increased O-GlcNAcase (OGA) level. RH increased brain inflammation and p-Tau and amyloid β accumulation, and these effects were suppressed by GlcN. Our observations collectively suggest that changes in O-GlcNAc flux during hypoxic exposure could be an important causal factor for neurodegeneration, and that supplementation of the HBP/ O-GlcNAc flux may be a potential novel therapeutic or preventive target for addressing hypoxic brain damage.

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BARBITURATE PROTECTION FOR HYPOXIC BRAIN DAMAGE

The Medical Journal of Australia ◽

10.5694/j.1326-5377.1980.tb76936.x ◽

1980 ◽

Vol 2 (3) ◽

pp. 114-115 ◽

Cited By ~ 1

Author(s):

Tess O'Rourke Brophy

Keyword(s):

Brain Damage ◽

Hypoxic Brain Damage ◽

Hypoxic Brain ◽

Barbiturate Protection

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Cardiac and Respiratory Arrest in a 12-Year-Old Girl with Acute Permethrin Toxicity: A Case Report

10.21203/rs.3.rs-305921/v2 ◽

2021 ◽

Author(s):

Hesam Adin Atashi ◽

Hamid Zaferani Arani ◽

Seyyed Mojtaba Ghorani ◽

Mahya Sadat Teimouri Khorasani ◽

Masoumeh Moalem

Keyword(s):

Case Report ◽

Brain Damage ◽

Respiratory Arrest ◽

Spontaneous Circulation ◽

Type I ◽

Medical Problems ◽

Present Case Report ◽

Case Presentation ◽

Hypoxic Brain Damage ◽

Hypoxic Brain

Abstract Background: Permethrin (PER) is widely employed as the most frequently used type I synthetic pyrethroid insecticide. Despite its worldwide application, reports of pediatric toxicity following permethrin administration are scarce.Case presentation: The present case report involves a 12-year-old Afghan girl, with no previous medical problems, who drank an unknown insecticide covertly at home. Two hours after ingestion, she was taken to the emergency room with neither breathing signs nor a heartbeat. She was immediately transferred to the cardiopulmonary resuscitation (CPR) room, and her spontaneous circulation was returned after a few minutes of CPR. She was then intubated, volume resuscitated with intravenous normal saline, and connected to the mechanical ventilator after being transferred to the ICU ward. The patient remained comatose without spontaneous breathing, her pupils became bilateral mydriasis, and central diabetes insipidus became evident after three days due to apnea and hypoxic brain damage following insecticide ingestion. The chemical analysis of the insecticide bottle showed 10% permethrin without organophosphates, as initially expected. Unfortunately, after seven days, the patient passed away due to resistant hypotension and severe brain damage.Conclusion: Permethrin is widely used globally as an insecticide. However, there are many unmet needs in permethrin toxicity treatment, and the treatment is mainly supportive. Depending on the amount and dose of permethrin, the most common symptoms can vary from headache, dyspnea, and vomiting to metabolic acidosis and cardiac and respiratory arrest, which can lead to hypoxic brain damage and death, as was the outcome in our case.

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