Propofol induces neuroapoptosis in the developing mouse brain

Drugs that suppress neuronal activity, including general anesthetics used in pediatric and obstetric medicine, trigger neuroapoptosis in the developing rodent brain. Brief exposure of infant mice to sub-anesthetic doses of any of several individual anesthetic drugs (ketamine, midazolam, isoflurane) triggers a significant neuroapoptosis response. Propofol, a general anesthetic currently being used with increasing frequency in pediatric and obstetric anesthesia, is a very effective suppressant of neuronal activity. Its mechanism of action is not fully understood; interaction with both GABAA receptors and NMDA glutamate receptors has been implicated. Propofol has not been evaluated for apoptogenic potential, either alone or in combination with other anesthetic agents. Therefore, we undertook the present study to determine whether propofol triggers neuroapoptosis in the infant mouse brain and, if so, what level of exposure is required to induce a significant neuroapoptosis response. In a dose-finding pilot study we determined that infant mice become unresponsive (loss of righting reflex) to deep pain (tail prick) at an intraperitoneal (ip) dose of approximately 200 mg/kg. A dose-response evaluation was then undertaken which revealed that any dose above 50 mg/kg ip induces a statistically significant neuroapoptosis response in several regions of the developing mouse brain. The magnitude of the response increased linearly in a dose dependent manner within the dose range tested (25 to 100 mg/kg ip). We conclude that a single sub-anesthetic (moderately sedating) dose of propofol triggers a significant neuroapoptosis response in the developing mouse brain

Acute inflammatory demyelinating polyneuropathy and a unilateral babinski/plantar reflex

Acquired acute demyelinating peripheral polyneuropathy (AADP) is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS). GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus) or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae). A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign). A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind

Xenon Upregulates Hypoxia Inducible Factor 1 Alpha in Neonatal Rat Brain under Normoxic Conditions

Xenon can induce cell and organ protection through different molecular mechanisms related to oxygen level. We explored the effect of xenon on oxygen-related signalling in the central nervous system via hypoxia inducible factor 1 alpha (HIF-1α) and mammalian target of rapamycin (mTOR). Methods. Postnatal day 7 (P7) Sprague Dawley rats were exposed to 25% oxygen/75% nitrogen (air group) or 25% oxygen/75% xenon (treatment group) for 120 min. Brains were collected immediately (transcript analysis—relative real-time polymerase chain reaction) or 24 hours (protein analysis—immunohistochemistry) after the 120-minute exposure period; peak anesthetic preconditioning has been previously identified at 24 hours post-exposure. Results. HIF-1α transcript and protein levels were found to be increased in xenon-exposed compared to air-exposed brains. Sustained nuclear translocation of the protein, accounting for an increased activity of HIF-1α, was also noted. mTOR transcript analysis revealed no significant difference between xenon-exposed and air-exposed brains immediately after the 120-minute exposure. Conclusion. Our data suggest that xenon induces the upregulation of HIF-1α transcription and translation, which may contribute to xenon's neuroprotective preconditioning effect. However, given that xenon exposure did not affect mTOR transcription, further investigation into other signalling cascades mediating xenon's effects on HIF-1α in developing brain is warranted