Neuroscience: The most vulnerable brains

Hayden, Erika Check

doi:10.1038/463154a

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…1,2 Approximately 30% of infants born preterm (<28 gestational weeks) will suffer from cerebral palsy (CP), cognitive impairment or neuropsychiatric disorders. [3][4][5] CP is the most common cause of severe disability in children (2/1000 births) and a major cost to sufferers, their families and society, 6,7 underscoring the need for development of treatment and preventive strategies.…”

Section: Introductionmentioning

confidence: 99%

Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection

Koning

Leverin

Nair

et al. 2017

J Cereb Blood Flow Metab

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Magnesium sulphate (MgSO) given to women in preterm labor reduces cerebral palsy in their offspring but the mechanism behind this protection is unclear, limiting its effective, safe clinical implementation. Previous studies suggest that MgSO is not neuroprotective if administered during or after the insult, so we hypothesised that MgSO induces preconditioning in the immature brain. Therefore, we administered MgSO at various time-points before/after unilateral hypoxia-ischemia (HI) in seven-day-old rats. We found that MgSO treatment administered as a bolus between 6 days and 12 h prior to HI markedly reduced the brain injury, with maximal protection achieved by 1.1 mg/g MgSO administered 24 h before HI. As serum magnesium levels returned to baseline before the induction of HI, we ascribed this reduction in brain injury to preconditioning. Cerebral blood flow was unaffected, but mRNAs/miRNAs involved in mitochondrial function and metabolism were modulated by MgSO. Metabolomic analysis (H-NMR) disclosed that MgSO attenuated HI-induced increases in succinate and prevented depletion of high-energy phosphates. MgSO pretreatment preserved mitochondrial respiration, reducing ROS production and inflammation after HI. Therefore, we propose that MgSO evokes preconditioning via induction of mitochondrial resistance and attenuation of inflammation.

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Section: Introductionmentioning

confidence: 99%

Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection

Koning

Leverin

Nair

et al. 2017

J Cereb Blood Flow Metab

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“…Neonatal neurocritical care has also recently emerged because of the specialized needs of critically ill newborns with brain injury. 25,26 Now, to address the needs of older children with acute brain injury, some child neurologists and pediatric intensivists have called for the development of pediatric neurocritical care as a subspecialty. 26 -28 It is unknown whether specialized pediatric neurocritical care would improve childhood stroke outcomes, but the high rates of critical care utilization and poor outcomes in our cohort suggest that research focused on the critical care management of childhood stroke would be vital to the care of the majority of these patients and support a need for further studies in this area.…”

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confidence: 99%

High critical care usage due to pediatric stroke

Fox

Fullerton

2012

Neurology

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Objectives: To measure intensive care unit (ICU) admission, intubation, decompressive craniotomy, and outcomes at discharge in a large population-based study of children with ischemic and hemorrhagic stroke. Methods:In a retrospective study of all children enrolled in a Northern Californian integrated health care plan (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003), we identified cases of symptomatic childhood stroke (age Ͼ28 days through 19 years) from inpatient and outpatient electronic diagnoses and radiology reports, and confirmed them through chart review. Data regarding stroke evaluation, management, and outcomes at discharge were abstracted. Intensive care unit (ICU) admission, intubation, and decompressive neurosurgery rates were measured, and multivariate logistic regression was used to identify predictors of critical care usage and outcomes at discharge. Results:Of 256 cases (132 hemorrhagic and 124 ischemic), 61% were admitted to the ICU, 32% were intubated, and 11% were treated with a decompressive neurosurgery. Rates were particularly high among children with hemorrhagic stroke (73% admitted to the ICU, 42% intubated, and 19% received a decompressive neurosurgery). Altered mental status at presentation was the most robust predictor for all 3 measures of critical care utilization. Neurologic deficits at discharge were documented in 57%, and were less common after hemorrhagic than ischemic stroke: 48% vs 66% (odds ratio 0.5, 95% confidence interval 0.3-0.8). Case fatality was 4% overall, 7% among children admitted to the ICU, and was similar between ischemic and hemorrhagic stroke.Conclusions: ICU admission is frequent after childhood stroke and appears to be justified by high rates of intubation and surgical decompression. Pediatric stroke occurs in 2-13/100,000 children annually, 1,2 and while hospital case series have reported high rates of neurologic deficits and case fatality, 3,4 data from population-based cohorts are limited. After a large stroke, neurologic deterioration may progress over several days from swelling, intracranial hypertension, and secondary brain injury. Although adult neurocritical care after a stroke has received increasing attention, little has been reported regarding critical care management practices of childhood stroke. However, children may have several reasons to require critical care management of elevated intracranial pressures: 1) children have a high proportion of hemorrhagic strokes, 1,5 2) ischemic strokes in children are predominantly large-vessel, 6,7 and 3) children lack the cerebral atrophy of aging that provides space to accommodate mass effect. We hypothesized that the frequency of ICU admission and interventions such as intubation and surgical decompression would be high after pediatric stroke, even in a

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“…Neonatal brain injury is a problem of great global concern [1, 2]. Advances in perinatal care have improved survival rates of affected infants, but long-term morbidity is still substantial [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Short-, Mid-, and Long-Term Effect of Granulocyte Colony-Stimulating Factor/Stem Cell Factor and Fms-Related Tyrosine Kinase 3 Ligand Evaluated in an In Vivo Model of Hypoxic-Hyperoxic Ischemic Neonatal Brain Injury

Posod

Wegleiter

Neubauer

et al. 2019

BioMed Research International

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Hematopoietic growth factors are considered to bear neuroprotective potential. We have previously shown that delayed treatment with granulocyte colony-stimulating factor (G-CSF)/stem cell factor (SCF) and Fms-related tyrosine kinase 3 ligand (FL) ameliorates excitotoxic neonatal brain injury. The effect of these substances in combined-stressor neonatal brain injury models more closely mimicking clinical conditions has not been investigated. The aim of this study was to assess the short-, mid-, and long-term neuroprotective potential of G-CSF/SCF and FL in a neonatal model of hypoxic-hyperoxic ischemic brain injury. Five-day-old (P5) CD-1 mice were subjected to unilateral common carotid artery ligation and subsequent alternating periods of hypoxia and hyperoxia for 65 minutes. Sixty hours after injury, pups were randomly assigned to intraperitoneal treatment with (i) G-CSF (200 μg/kg)/SCF (50 μg/kg), (ii) FL (100 μg/kg), or (iii) vehicle every 24 hours for three or five consecutive days. Histopathological and functional outcomes were evaluated on P10, P18, and P90. Baseline outcome parameters were established in sham-treated and healthy control animals. Gross brain injury did not significantly differ between treatment groups at any time point. On P10, caspase-3 activation and caspase-independent apoptosis were similar between treatment groups; cell proliferation and the number of BrdU-positive vessels did not differ on P18 or P90. Neurobehavioral assessment did not reveal significant differences between treatment groups in accelerod performance, open field behavior, or novel object recognition capacity on P90. Turning behavior was more frequently observed in G-CSF/SCF- and FL-treated animals. No sex-specific differences were detected in any outcome parameter evaluated. In hypoxic-hyperoxic ischemic neonatal brain injury, G-CSF/SCF and FL treatment does not convey neuroprotection. Prior to potential clinical use, meticulous assessment of these hematopoietic growth factors is mandated.

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Neuroscience: The most vulnerable brains

Cited by 3 publications

References 8 publications

Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection

Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection

High critical care usage due to pediatric stroke

Short-, Mid-, and Long-Term Effect of Granulocyte Colony-Stimulating Factor/Stem Cell Factor and Fms-Related Tyrosine Kinase 3 Ligand Evaluated in an In Vivo Model of Hypoxic-Hyperoxic Ischemic Neonatal Brain Injury

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