Caffeine Protects Against Anticonvulsant-Induced Impaired Neurogenesis in the Developing Rat Brain

Endesfelder, Stefanie; Weichelt, Ulrike; Schiller, Cornelia; Winter, Katja; Haefen, Clarissa von; Bührer, Christoph

doi:10.1007/s12640-018-9872-8

Cited by 19 publications

(21 citation statements)

References 107 publications

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“…The gene expression analysis was performed as previously described [37]. The PCR products of hypoxanthine-guanine phosphoribosyl-transferase (Hprt), Kelch-like ECH-associated protein 1 (Keap1), NFE2-related factor 2 (Nrf2), and superoxide dismutase (Sod) 1, 2, and 3 were quantified in real time with the sequences (synthesized by BioTeZ, Berlin, Germany) summarized in Additional file 2: Table S1.…”

Section: Rna Extraction and Quantitative Real-time Pcrmentioning

confidence: 99%

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

et al. 2019

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Background: While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats. Methods: Newborn Wistar rats were exposed to 21% or 80% oxygen for 3 (P3) or 5 (P5) postnatal days with or without recovery on room air until postnatal day 15 (P15) and treated with vehicle or caffeine (10 mg/kg) every 48 h beginning on the day of birth. The lung tissue of the rat pups was examined for oxidative stress response at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR. Results: Lungs of newborn rats, corresponding to the saccular stage of lung development and to the human lung developmental stage of preterms, showed increased rates of total glutathione and hydrogen peroxide, oxidative damage to DNA and lipids, and induction of second-phase mediators of antioxidative stress response (superoxide dismutase, heme oxygenase-1, and the Nrf2/Keap1 system) in response to hyperoxia. Caffeine reduced oxidative DNA damage and had a protective interference with the oxidative stress response. Conclusion: In addition to the pharmacological antagonism of adenosine receptors, caffeine appears to be a potent antioxidant and modulates the hyperoxia-induced pulmonary oxidative stress response and thus protective properties in the BPD-associated animal model. Free-radical-induced damage caused by oxidative stress seems to be a biological mechanism progress of newborn diseases. New aspects of antioxidative therapeutic strategies to passivate oxidative stress-related injury should be in focus of further investigations.

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Section: Rna Extraction and Quantitative Real-time Pcrmentioning

confidence: 99%

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

et al. 2019

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“…More recent data, from animal studies, have shown that Caffeine administered with Phenobarbital decreased the negative effects of Phenobarbital on neural cells. 36 In our study, nearly all infants with seizures treated with Phenobarbital were receiving Caffeine for apnea of prematurity.…”

Section: Discussionmentioning

confidence: 72%

Seizures in Pre-term Infants Less than 29 Weeks: Incidence, Etiology, and Response to Treatment

Raghuveer¹,

Zackula²,

Gibson³

et al. 2020

kjm

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Introduction. Seizures are neurological emergencies with short- and long-term adverse effects in pre-term infants. They may present with or without abnormal movements (clinical versus subclinical). Thus, the true incidence of seizures may be under-reported. Current research indicates that most seizures occur in the first few days of life, are associated with intraventricular hemorrhage (IVH), and show low response to anticonvulsant drugs. The purpose of this study was to evaluate incidence, etiology, clinical antecedents, mortality, and response to treatment of seizures in extremely pre-term infants. Methods. This is a retrospective cohort study of pre-term infants < 29 weeks gestation from January 2011 to December 2013. Presence or absence of seizure was the outcome. Data extraction included demographics, medications, co-morbidities, mortality, and details of seizures. A multivariable prediction model was developed to evaluate risk for seizures. Results. Analysis included 269 pre-term infants. Incidence of EEG-confirmed seizures was 40% (108/269); 49% were clinical and 51% were subclinical. Seizures occurred in 72% of infants ≤ 24 weeks, 57% of those 25-26 weeks, and 23% of those 27-28 weeks. Most seizures (85%) occurred after day eight of life. Mortality was 14% in those with seizures versus 5% in those without (p = 0.019). The model showed seizures were associated significantly with gestational age and medications, while controlling for sex, APGAR score, and co-morbidities, including IVH. At discharge, anticonvulsants were continued in 66% (72/108) of infants with seizures. Conclusion. The incidence of seizures was highest in infants born most premature. Contrary to previous research, nearly two-thirds of pre-term infants with seizures did not have IVH or cystic periventricular leukomalacia; apnea of prematurity was a common presentation of subclinical seizures; and the majority of treated infants responded to Phenobarbital. These findings need be explored in future research.

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“…Likewise, only the effect of caffeine, an A1 antagonist, on neurodevelopment has been studied. Caffeine is shown to ameliorate phenobarbital impairment of neurogenesis in neonatal rats [287], possibly due to caffeine's ability to suppress GABAergic action [288]. However, when it is given in isolation, caffeine reduces the proliferative capacity of the brain [287].…”

Section: Targeting Of P1 Receptorsmentioning

confidence: 99%

“…Caffeine is shown to ameliorate phenobarbital impairment of neurogenesis in neonatal rats [287], possibly due to caffeine's ability to suppress GABAergic action [288]. However, when it is given in isolation, caffeine reduces the proliferative capacity of the brain [287]. In the adult mouse, caffeine can reduce long-term potentiation and can alter synaptic plasticity, which could be detrimental in the immature brain [289].…”

Section: Targeting Of P1 Receptorsmentioning

confidence: 99%

Neonatal Seizures and Purinergic Signalling

Méndez¹,

Smith

Engel

2020

IJMS

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Neonatal seizures are one of the most common comorbidities of neonatal encephalopathy, with seizures aggravating acute injury and clinical outcomes. Current treatment can control early life seizures; however, a high level of pharmacoresistance remains among infants, with increasing evidence suggesting current anti-seizure medication potentiating brain damage. This emphasises the need to develop safer therapeutic strategies with a different mechanism of action. The purinergic system, characterised by the use of adenosine triphosphate and its metabolites as signalling molecules, consists of the membrane-bound P1 and P2 purinoreceptors and proteins to modulate extracellular purine nucleotides and nucleoside levels. Targeting this system is proving successful at treating many disorders and diseases of the central nervous system, including epilepsy. Mounting evidence demonstrates that drugs targeting the purinergic system provide both convulsive and anticonvulsive effects. With components of the purinergic signalling system being widely expressed during brain development, emerging evidence suggests that purinergic signalling contributes to neonatal seizures. In this review, we first provide an overview on neonatal seizure pathology and purinergic signalling during brain development. We then describe in detail recent evidence demonstrating a role for purinergic signalling during neonatal seizures and discuss possible purine-based avenues for seizure suppression in neonates.

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Caffeine Protects Against Anticonvulsant-Induced Impaired Neurogenesis in the Developing Rat Brain

Cited by 19 publications

References 107 publications

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

Seizures in Pre-term Infants Less than 29 Weeks: Incidence, Etiology, and Response to Treatment

Neonatal Seizures and Purinergic Signalling

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