International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
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Int. J. Dev. Neurosci. · May 2020
Protective effects of Coenzyme Q10 against sevoflurane-induced cognitive impairment through regulating apolipoprotein E and phosphorylated Tau expression in young mice.
Children with multiple exposures to anesthesia and surgery may be more likely to develop the learning disability. Coenzyme Q10 (CoQ10) was reported to reduce the multiple sevoflurane treatment-induced cognitive deficiency in 6-day-old young mice. However, its specific mechanisms have not yet been found. ⋯ The results indicated that the injection of CoQ10 ahead of sevoflurane treatment could reverse the anesthesia-induced energy deficiency, mitochondrial dysfunction, ApoE, and its fragments expression, Aβ1-42 generation, Tau phosphorylation, and cognitive impairment in young mice. These data reveal that the ApoE and its fragments enhancement may play an important role in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia. CoQ10 could reduce ApoE expression by improving energy replenishment and mitochondrial functions, thereby alleviating sevoflurane-induced brain damage and cognitive impairment.
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Int. J. Dev. Neurosci. · Aug 2019
Neuroglobin protects offspring rats from neuronal damage induced by sevoflurane exposure to pregnant rats by inhibiting endogenous apoptosis.
As a general anesthesia drug, sevoflurane has been found to be potentially neurotoxic to the developing brain. Neuroglobin (Ngb) is a novel oxygen-carrying globulin that has been demonstrated to have neuroprotective effects in a variety of central nervous system disorders. However, it is unclear whether Ngb has a protective effect on nerve damage caused by sevoflurane. ⋯ We concluded that Ngb can improve the neuronal injury induced by sevoflurane exposure by inhibiting apoptosis and increasing the number of neurons. And this protective effect of Ngb may be related to Hif-1α signaling pathway. This finding may provide a novel therapeutic approach for sevoflurane -induced nerve damage.
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Int. J. Dev. Neurosci. · Jun 2019
Dexmedetomidine reduced sevoflurane-induced neurodegeneration and long-term memory deficits in neonatal rats.
Exposure to sevoflurane and other inhalational anesthetics can induce neurodegeneration in the developing brain. Although dexmedetomidine (DEX) has provided neuroprotection against hypoxic ischemic injury, relatively little is known about whether it has the neuroprotective effects against anesthetic-induced neurodegeneration. This study examined whether DEX improves the long-term cognitive dysfunction observed after exposure of neonatal rats to 3% sevoflurane. ⋯ The freezing times of the DEX 0 and 6.6 groups were significantly decreased compared with those in the sham, control and DEX 25 groups. The number of NeuN-positive cells in the CA1 region was significantly decreased in the DEX 0 and 6.6 groups compared with the sham, control and DEX 25 groups. These findings indicate pre-treatment with DEX may improve long-term cognitive function and ameliorate the neuronal degeneration induced by sevoflurane exposure in neonatal rats.
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Int. J. Dev. Neurosci. · Dec 2018
NGF, TrkA-P and neuroprotection after a hypoxic event in the developing central nervous system.
A decrease in the concentration of oxygen in the blood and tissues (hypoxia) produces important, sometimes irreversible, damages in the central nervous system (CNS) both during development and also postnatally. The present work aims at analyzing the expression of nerve growth factor (NGF) and p75 and the activation of TrkA in response to an acute normobaric hypoxic event and to evaluate the possible protective role of exogenous NGF. The developing chick optic tectum (OT), a recognized model of corticogenesis, was used as experimental system by means of in vivo and in vitro studies. ⋯ Interestingly, this cell death can be reverted if TrkA inactivation during hypoxia is suppressed by the addition of NGF. Our results suggest that TrkA activation may play an important role in the survival of OT neurons subjected to acute hypoxia. The role of TrkA in neuronal survival after injury may be advantageously used for the generation of neuroprotective strategies to improve prenatal insult outcomes.
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Int. J. Dev. Neurosci. · Nov 2018
Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.
Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. ⋯ These findings suggested that the enhancement of intrinsic neurotransmitter NE signaling by a selective NE reuptake inhibitor, atomoxetine, reduced the perinatal HI insult brain injury. In addition, atomoxetine treatment was associated with changes of TUNEL, pCREB, and BDNF expression levels, and microglial numbers, morphology, and responses.