General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain

Lu, Lucy X.; Yon, Jun Heum; Carter, Lisa B.; Jevtović-Todorović, Vesna

doi:10.1007/s10495-006-8762-3

Cited by 218 publications

(194 citation statements)

References 33 publications

(46 reference statements)

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“…We feel that alterations in these variables are extremely unlikely to explain the plasticity given that extensive previous studies have not demonstrated such events using exactly the same protocols (Jevtovic-Todorovic et al, 2003;Lu et al, 2006;Rizzi et al, 2008;Loepke et al, 2009). We used a triple combination of potent volatile anesthetic agents: 0.75 vol% Iso supplemented with 75 vol% N 2 O and 9 mg/kg midazolam be- Figure 9.…”

Section: Discussionmentioning

confidence: 86%

Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development

DiGruccio

Joksimović

Joksovic³

et al. 2015

J. Neurosci.

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Prevailing literature supports the idea that common general anesthetics (GAs) cause long-term cognitive changes and neurodegeneration in the developing mammalian brain, especially in the thalamus. However, the possible role of GAs in modifying ion channels that control neuronal excitability has not been taken into consideration. Here we show that rats exposed to GAs at postnatal day 7 display a lasting reduction in inhibitory synaptic transmission, an increase in excitatory synaptic transmission, and concomitant increase in the amplitude of T-type calcium currents (T-currents) in neurons of the nucleus reticularis thalami (nRT). Collectively, this plasticity of ionic currents leads to increased action potential firing in vitro and increased strength of pharmacologically induced spike and wave discharges in vivo. Selective blockade of T-currents reversed neuronal hyperexcitability in vitro and in vivo. We conclude that drugs that regulate thalamic excitability may improve the safety of GAs used during early brain development.

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Section: Discussionmentioning

confidence: 86%

Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development

DiGruccio

Joksimović

Joksovic³

et al. 2015

J. Neurosci.

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“…It is important to note that the reasons for the disparity between the two states in this study are likely multifaceted and may result from differences in stress levels, auditory arousal, and the effect of anesthetics. Indeed, volatile anesthesia (such as isoflurane) decreases excitatory and increases inhibitory transmission (Gomez and Guatimosim, 2003;Ouyang and Hemmings, 2005), affects neuroplasticity, and can alter BDNF expression (Lu et al, 2006;Head et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Markers for Neuroplasticity: Differential Outcomes in Anesthetized and Awake Animals

Gersner

Kravetz

Feil³

et al. 2011

J. Neurosci.

244

181

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Long-term effects of repetitive transcranial magnetic stimulation (rTMS) have been associated with neuroplasticity, but most physiological studies have evaluated only the immediate effects of the stimulation on neurochemical markers. Furthermore, although it is known that baseline excitability state plays a major role in rTMS outcomes, the role of spontaneous neural activity in metaplasticity has not been investigated. The first aim of this study was to evaluate and compare the long-term effects of high-and low-frequency rTMS on the markers of neuroplasticity such as BDNF and GluR1 subunit of AMPA receptor. The second aim was to assess whether these effects depend on spontaneous neural activity, by comparing the neurochemical alterations induced by rTMS in anesthetized and awake rats. Ten daily sessions of high-or low-frequency rTMS were applied over the rat brain, and 3 d later, levels of BDNF, GluR1, and phosphorylated GluR1 were assessed in the hippocampus, prelimbic cortex, and striatum. We found that high-frequency stimulation induced a profound effect on neuroplasticity markers; increasing them in awake animals while decreasing them in anesthetized animals. In contrast, low-frequency stimulation did not induce significant long-term effects on these markers in either state. This study highlights the importance of spontaneous neural activity during rTMS and demonstrates that high-frequency rTMS can induce long-lasting effects on BDNF and GluR1 which may underlie the clinical benefits of this treatment in neuroplasticity-related disorders.

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“…Exposure of 7-d-old rats to midazolamnitrous oxide-isoflurane anesthesia for 6 h led to widespread neurodegeneration and this was accompanied by persistent learning deficits (30). Anesthesia-induced activation of apoptotic pathways in immature neurons implicates significant changes in the expression pattern of brain-derived neurotrophic factor (BDNF) in the brain of rat pups (75).…”

Section: Experimental Data On the Effects Of Analgesics And Sedative mentioning

confidence: 99%

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

et al. 2010

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Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

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General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain

Cited by 218 publications

References 33 publications

Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development

Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development

Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Markers for Neuroplasticity: Differential Outcomes in Anesthetized and Awake Animals

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

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