Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model

Harman, Ferhat; Hastürk, Aşkın Esen; Yaman, Mehmet; Arca, Turkan; Kılınç, Kamer; Sargon, Mustafa F.; Kaptanoğlu, Erkan

doi:10.1007/s00381-012-1782-0

Cited by 44 publications

(29 citation statements)

References 37 publications

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“…Midazolam, a benzodiazepine, is commonly used for anesthesia and sedation in the intensive care unit and the operating room where there is a risk of cerebral ischemia. Recent researches mostly focused on the effects of midazolam on neuroprotection after transient focal cerebral ischemia [39]. However, till now, the cytoprotective effect of midazolam on brain astrocytes has not been clarified in detail.…”

Section: Discussionmentioning

confidence: 99%

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Liu

You²,

Tu³

et al. 2015

Cell Physiol Biochem

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Background: There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. Methods: The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay. Results: Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ. Conclusion: Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.

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Section: Discussionmentioning

confidence: 99%

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Liu

You²,

Tu³

et al. 2015

Cell Physiol Biochem

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“…Flumazenil reduces the seizure threshold [70], and seizure activity is thought to be part of the injurious process after HI in neonates [71]. Midazolam and naloxone have also been shown to be neuroprotective in some rodent models of stroke [72,73]. Despite these potential effects, we chose to use the sedative drugs rather than the more commonly described halothane or isoflurane - which have also been described as potentially neuroprotective by providing a preconditioning effect [74] - as fentanyl and midazolam are also often used in human asphyxiated newborns and reproduce more accurately what the newborns are going through.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups

et al. 2016

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Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

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“…Although there is some evidence of neuroprotective effects of magnesium in the preterm fetus, the role of magnesium as a neuroprotective agent in the pregnant patient undergoing a neurosurgical procedure would be an area for further research. 19 During the time of temporary clipping (ischemia), electroencephalographic burst suppression can be achieved with use of intravenous propofol.…”

Section: Neuroprotectionmentioning

confidence: 99%

“…Bien qu'il existe des données probantes démontrant un effet neuroprotecteur du magnésium sur le foetus avant terme, le rôle du magnésium en tant qu'agent neuroprotecteur chez la femme enceinte subissant une intervention neurochirurgicale nécessite davantage de recherches. 19 Pendant le clampage temporaire (ischémie), on peut réaliser un test de « burst suppression » électroencéphalographique à l'aide de propofol intraveineux.…”

Section: Considérations Hémodynamiquesunclassified

Perioperative considerations for neurosurgical procedures in the gravid patient: Continuing Professional Development

Chowdhury

Schaller

et al. 2013

Can J Anesth/J Can Anesth

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Purpose The complexity of neurosurgical procedures and their interactions with maternal and fetal physiologies are key factors in determining the overall maternal and fetal outcome. The literature and guidelines provide only partial information regarding the standard of care in these cases. The purpose of this Continuing Professional Development module is to review the issues related to common neurosurgical conditions and their optimal anesthetic management. Principal findings The most common neurosurgical conditions found in pregnancy include brain tumours, cerebrovascular diseases, spinal pathologies, and neurotrauma. Though rare, these conditions and related procedures may affect maternal and fetal outcome. Maternal considerations should be given priority in cases of emergent surgeries irrespective of trimester. In the early first trimester, risk of fetal loss and congenital malformation are substantial; hence, proper counselling should be given to the mother with special emphasis on therapeutic abortion. When indicated, anticonvulsants should be started as early as possible and continued throughout pregnancy. Surgical procedures can be performed with relative safety during the second trimester and early third trimester. After 34 weeks, delivery seems to be the first choice, and the role of regional anesthesia in this situation should be carefully planned after proper review of neurosurgical pathology and maternal condition. During acute neurological deterioration, however, Cesarean delivery under general anesthesia should be anticipated. Conclusion A multidisciplinary approach with good communication amongst all team members certainly plays a crucial role for successful management of such cases.

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Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model

Abstract: Propofol and midazolam may be used to protect fetal brain in case of acute fetal distress and hypoxic injury as a first choice anesthetic drug in cesarean delivery.

Cited by 44 publications

References 37 publications

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups

Perioperative considerations for neurosurgical procedures in the gravid patient: Continuing Professional Development

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