Early malnutrition attenuates the impairing action of naloxone on spreading depression in young rats

Guedes, Rubem Carlos Araújo; Rocha-de-Melo, Ana Paula; Lima, Kalina Rimena de; Albuquerque, Juliana da Mota Silveira de; Francisco, Elian da Silva

doi:10.1179/1476830512y.0000000046

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…The diversity of anti-SD substances underlines the complexity of SD and indicates that more research is necessary. Table 5 shows that some of the substances that are less known for an inhibitory effect against SD (naloxone, 230,231 GYKI 52466, 232,233 sulpiride, 234 and THC 235 ) show potential to reduce SD number, propagation, and duration and must not be forgotten.…”

Section: Sumatriptanmentioning

confidence: 99%

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Klass

Sánchez-Porras

Santos

2018

J Cereb Blood Flow Metab

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Spreading depolarization (SD) occurs alongside brain injuries and it can lead to neuronal damage. Therefore, pharmacological modulation of SD can constitute a therapeutic approach to reduce its detrimental effects and to improve the clinical outcome of patients. The major objective of this article was to produce a systematic review of all the drugs that have been tested against SD. Of the substances that have been examined, most have been shown to modulate certain SD characteristics. Only a few have succeeded in significantly inhibiting SD. We present a variety of strategies that have been proposed to overcome the notorious harmfulness and pharmacoresistance of SD. Information on clinically used anesthetic, sedative, hypnotic agents, anti-migraine drugs, anticonvulsants and various other substances have been compiled and reviewed with respect to the efficacy against SD, in order to answer the question of whether a drug at safe doses could be of therapeutic use against SD in humans.

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Section: Sumatriptanmentioning

confidence: 99%

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Klass

Sánchez-Porras

Santos

2018

J Cereb Blood Flow Metab

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“…The CSD recording sessions were conducted under i.p. anesthesia using a mixture of 1 g/kg urethane plus 40 mg/kg chloralose (Sigma) as previously described (Abadie-Guedes et al, 2008; Guedes et al, 2013, 2017). Three trephine holes were made on the ipsilateral side of the skull, parallel to the midline.…”

Section: Methodsmentioning

confidence: 99%

“…The cotton ball was used for 30 min, and recording continued for up to 2 or 6 h (for the short and long recording groups, respectively). The changes in slow direct current potential (DC potential) and the decrease in spontaneous cortical electrical activity associated with CSD were continuously recorded at the 2 parietal holes using a pair of Ag/AgCl agar-Ringer electrodes, as described previously (Abadie-Guedes et al, 2008; Guedes et al, 2013; Mo et al, 2015) (Figure 1). Both holes for the application of KCl and the placement of the 2 electrodes were made on the intact dura mater.…”

Section: Methodsmentioning

confidence: 99%

“…Due to the massive and synchronous depolarization of neurons and glia that occur during CSD, some authors have opted for the term spreading depolarization, highlighting that the depression of cellular activity that follows the CSD wave is also important (Leao, 1947; Kadam and Dudek, 2016). CSD can be observed in damaged brain regions and is related to neurological disorders, such as migraine aura (Fabricius et al, 2006; Hosseini-Zare et al, 2017), brain trauma (Lauritzen et al, 2011; Hosseini-Zare et al, 2017) and epileptic seizures, but it can also be induced experimentally using chemical stimulation (Guedes et al, 2013, 2017; Torrente et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Stereological Analysis of Early Gene Expression Using Egr-1 Immunolabeling After Spreading Depression in the Rat Somatosensory Cortex

et al. 2019

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Early growth response-1 (Egr-1), defined as a zinc finger transcription factor, is an upstream master switch of the inflammatory response, and its expression can be used to investigate the spatial and temporal extent of inflammatory changes in the brain. Cortical spreading depression (CSD) is characterized as a slowly propagating (2–5 mm/min) depolarization wave through neurons and astrocytes in humans that contributes to migraines and possibly to other brain pathologies. In rodents, CSD can be induced experimentally, which involves unilateral depolarization that is associated with microglial and astrocyte responses. The impact of CSD on structures beyond the affected hemisphere has not been explored. Here, we used an optical fractionator method to investigate potential correlations between the number of and period of the eletrophysiologic record of CSD phenomena and Egr-1 expression in ipsilateral and contralateral hemispheres. CSD was elicited by the restricted application of a 2% KCl solution over the left premotor cortex. Electrophysiological events were recorded using a pair of Ag/AgCl agar-Ringer electrodes for 2 or 6 h. An optical fractionator was applied to count the Egr-1 positive cells. We found that CSD increased Egr-1 expression in a time- and event-dependent manner in the ipsilateral/left hemisphere. Although CSD did not cross the midline, multiple CSD inductions were associated with an increased number of Egr-1 positive cells in the contralateral/right hemisphere. Thus, repeated CSD waves may have far reaching effects that are more global than previously considered possible. The mechanism of contralateral expression is unknown, but we speculate that callosal projections from the depolarized hemisphere may be related to this phenomenon.

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Neonatal l-glutamine modulates anxiety-like behavior, cortical spreading depression, and microglial immunoreactivity: analysis in developing rats suckled on normal size- and large size litters

et al. 2016

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In mammals, L-glutamine (Gln) can alter the glutamate-Gln cycle and consequently brain excitability. Here, we investigated in developing rats the effect of treatment with different doses of Gln on anxiety-like behavior, cortical spreading depression (CSD), and microglial activation expressed as Iba1-immunoreactivity. Wistar rats were suckled in litters with 9 and 15 pups (groups L and L; respectively, normal size- and large size litters). From postnatal days (P) 7-27, the animals received Gln per gavage (250, 500 or 750 mg/kg/day), or vehicle (water), or no treatment (naive). At P28 and P30, we tested the animals, respectively, in the elevated plus maze and open field. At P30-35, we measured CSD parameters (velocity of propagation, amplitude, and duration). Fixative-perfused brains were processed for microglial immunolabeling with anti-IBA-1 antibodies to analyze cortical microglia. Rats treated with Gln presented an anxiolytic behavior and accelerated CSD propagation when compared to the water- and naive control groups. Furthermore, CSD velocity was higher (p< 0.001) in the L compared to the L condition. Gln treatment increased Iba1 immunolabeling both in the parietal cortex and CA1 hippocampus, indicating microglial activation. The Gln effect was dose-dependent for anxiety-like behavior and CSD in both litter sizes, and for microglial activation in the L groups. Besides confirming previous electrophysiological findings (CSD acceleration after Gln), our data demonstrate for the first time a behavioral and microglial activation that is associated with early Gln treatment in developing animals, and that is possibly operated via changes in brain excitability.

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Early malnutrition attenuates the impairing action of naloxone on spreading depression in young rats

Abstract: Data strongly support the involvement of opioid-based mechanisms in excitability-related neural processes, which probably influence CSD propagation, and indicate that early malnutrition attenuates the impairing action of naloxone on CSD.

Cited by 7 publications

References 41 publications

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Stereological Analysis of Early Gene Expression Using Egr-1 Immunolabeling After Spreading Depression in the Rat Somatosensory Cortex

Neonatal l-glutamine modulates anxiety-like behavior, cortical spreading depression, and microglial immunoreactivity: analysis in developing rats suckled on normal size- and large size litters

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