Possible Neuroprotective Effects of Magnesium Sulfate and Melatonin as Both Pre- and Post-Treatment in a Neonatal Hypoxic-Ischemic Rat Model

Çetınkaya, Merih; Alkan, Tülin; Özyener, Fadıl; Kafa, İ̇lker Mustafa; Kurt, Mustafa Ayberk; Köksal, Nilgün

doi:10.1159/000320643

Cited by 52 publications

(42 citation statements)

References 78 publications

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“…The most promising ones are xenon [19,20], erythropoietin [21,22,23] and melatonin [18,24], which are currently undergoing preclinical studies, feasibility studies or small randomized controlled studies [21,25]. Whatever the outcome from combination therapy, it is important to further optimize HT used as the sole intervention.…”

Section: Discussionmentioning

confidence: 99%

Time Is Brain: Starting Therapeutic Hypothermia within Three Hours after Birth Improves Motor Outcome in Asphyxiated Newborns

et al. 2013

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Objective: Therapeutic hypothermia (HT) is the standard treatment for newborns after perinatal asphyxia. Preclinical studies report that HT is more effective when started early. Methods: Eighty cooled newborns were analyzed and grouped according to when cooling was started after birth: early (≤180 min) or late (>181 min). For survivors we analyzed whether starting cooling early was associated with a better psychomotor or mental developmental index (PDI or MDI, Bayley Scales of Infant Development II) than late cooling. Results: Forty-three newborns started cooling early and 37 started late. There was no significant difference in the severity markers of perinatal asphyxia between the groups; however, nonsurvivors (n = 15) suffered more severe asphyxia and had significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that survived, 35 were cooled early and 30 were cooled late. There was no difference in time to start cooling between those who survived and those who did not. For survivors, median PDI (IQR) was significantly higher when cooled early [90 (77-99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no increase in cardiovascular adverse effects in those cooled early. There was no significant difference in MDI between early and late cooling [93 (77-103) vs. 89 (76-106), p = 0.594]. Conclusion: Starting cooling before 3 h of age in surviving asphyxiated newborns is safe and significantly improves motor outcome. Cooling should be initiated as soon as possible after birth in eligible infants.

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Section: Discussionmentioning

confidence: 99%

Time Is Brain: Starting Therapeutic Hypothermia within Three Hours after Birth Improves Motor Outcome in Asphyxiated Newborns

et al. 2013

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“…Seven (47%) of the perinatal studies surveyed reported improved neural outcomes with magnesium treatment alone (table 1) [20,21,22,23,24,25,26]. In 3 studies, MgSO 4 was given before the start of HI [20,21,22].…”

Section: Analysis Strategymentioning

confidence: 99%

“…In 3 studies, MgSO 4 was given before the start of HI [20,21,22]. In 4/7 studies, treatment was begun immediately after HI [24,25] or within 1.5 h [23,26].…”

Section: Analysis Strategymentioning

confidence: 99%

Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review

et al. 2014

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There is an important unmet need to further improve the outcome of neonatal encephalopathy in term infants. Meta-analyses of large controlled trials now suggest that maternal magnesium sulfate (MgSO₄) therapy is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth, but that it has no effect on death or disability. Because of this inconsistency, it remains controversial whether MgSO₄ is clinically neuroprotective and, thus, it is unclear whether it would be appropriate to test MgSO₄ for treatment of encephalopathy in term infants. We therefore systematically reviewed the preclinical evidence for neuroprotection with MgSO₄ before or after hypoxic-ischemic encephalopathy (HIE) in term-equivalent perinatal and adult animals. The outcomes were highly inconsistent between studies. Although there were differences in dose and timing of administration, there was evidence that beneficial effects of MgSO₄ were associated with confounding mild hypothermia and, strikingly, the studies that included rigorous maintenance of environmental temperature or body temperature consistently suggested a lack of effect. On balance, these preclinical studies suggest that peripherally administered MgSO₄ is unlikely to be neuroprotective. Rigorous testing in translational animal models of perinatal HIE is needed before MgSO₄ should be considered in clinical trials for encephalopathy in term infants.

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“…Drugs were intraperitoneally administered, and nicotine, resveratrol and DHA were administered before the hypoxic event while melatonin was administered 10 minutes after the hypoxic event (Table 1). (9) Saline and DMSO 5% 10 min after hypoxia (3,9,11). Resveratrol 20 (74) DMSO 10 min before hypoxia (25, 74) Docosahexaenoic acid 1 (7) HSA 25% diluted in normal saline 10 min before hypoxia (51) The time intervals of treatment injections pre-and post-HI and treatment doses were selected because of the existing good results for rat data on other brain areas after a perinatal asphyxia.…”

Section: Experimental Groupsmentioning

confidence: 99%

“…DHA was previously described as neuroprotective antioxidant when administered 1 or 3h before the HI event (51), resveratrol when given 10-15 minutes before (25,74), and nicotine 2 h before the damage (14). Meanwhile, melatonin is neuroprotective when administered just after the damage (3,9,11).…”

Section: Experimental Groupsmentioning

confidence: 99%

Antioxidant Treatments Recover the Alteration of Auditory‐Evoked Potentials and Reduce Morphological Damage in the Inferior Colliculus after Perinatal Asphyxia in Rat

et al. 2015

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Maturation of the auditory pathway is dependent on the central nervous system myelination and it can be affected by pathologies such as neonatal hypoxic ischemic (HI) encephalopathy. Our aim was to evaluate the functional integrity of the auditory pathway and to visualize, by histological and cellular methods, the damage to the brainstem using a neonatal rat model of HI brain injury. To carry out this morphofunctional evaluation, we studied the effects of the administration of the antioxidants nicotine, melatonin, resveratrol and docosahexaenoic acid after hypoxia-ischemia on the inferior colliculus and the auditory pathway. We found that the integrity of the auditory pathway in the brainstem was altered as a consequence of the HI insult. Thus, the auditory brainstem response (ABR) showed increased I-V and III-V wave latencies. At a histological level, HI altered the morphology of the inferior colliculus neurons, astrocytes and oligodendricytes, and at a molecular level, the mitochondria membrane potential and integrity was altered during the first hours after the HI and reactive oxygen species (ROS) activity is increased 12 h after the injury in the brainstem. Following antioxidant treatment, ABR interpeak latency intervals were restored and the body and brain weight was recovered as well as the morphology of the inferior colliculus that was similar to the control group. Our results support the hypothesis that antioxidant treatments have a protective effect on the functional changes of the auditory pathway and on the morphological damage which occurs after HI insult.

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Possible Neuroprotective Effects of Magnesium Sulfate and Melatonin as Both Pre- and Post-Treatment in a Neonatal Hypoxic-Ischemic Rat Model

Cited by 52 publications

References 78 publications

Time Is Brain: Starting Therapeutic Hypothermia within Three Hours after Birth Improves Motor Outcome in Asphyxiated Newborns

Time Is Brain: Starting Therapeutic Hypothermia within Three Hours after Birth Improves Motor Outcome in Asphyxiated Newborns

Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review

Antioxidant Treatments Recover the Alteration of Auditory‐Evoked Potentials and Reduce Morphological Damage in the Inferior Colliculus after Perinatal Asphyxia in Rat

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