Remote ischemic postconditioning for neuroprotection after newborn hypoxia–ischemia: systematic review of preclinical studies

Andelius, Ted Carl Kejlberg; Henriksen, Tine Brink; Kousholt, Birgitte S.; Kyng, Kasper Jacobsen

doi:10.1038/s41390-021-01656-7

Cited by 5 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are indications however, that neuroprotection in newborn animal models may require a longer duration of RIPC, as neonatal skeletal muscle and its endothelium may be more tolerant of low flow. In a 2021 review of preclinical studies of RIPC after newborn HI by our group, four out of five studies used 4 cycles of 10 min RIPC ( 22 ). Thus, RIPC amelioration of serum NfL derived from axonal disruption may require a longer RIPC cycle duration.…”

Section: Discussionmentioning

confidence: 99%

Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model

et al. 2023

View full text Add to dashboard Cite

AimNeurofilament light Chain (NfL) is a promising brain injury biomarker which may assist diagnosis and prognostication in hypoxic-ischemic encephalopathy (HIE). The aim of this study was to investigate serum NfL levels after hypoxia-ischemia (HI) in a newborn piglet model. Second, to characterize the influence of sex, weight, and treatment with remote ischemic postconditioning (RIPC) on NfL and the correlation between NfL, brain imaging and histologic brain injury.MethodsWe used serum from 48 newborn piglets of both sexes subjected to 45 min of global HI, and 4 sham piglets. Blood was collected pre-HI, 2 h post-HI and 72 h post-HI. NfL was measured by single-molecule array (Simoa™). We analysed the temporal profile of NfL after HI, and correlations between NfL, magnetic resonance spectroscopy brain Lac/NAA ratios and histologic brain injury 72 h after HI.ResultsMedian (IQR) NfL levels were: pre-HI: 66 pg/ml (45–87), 2 h post-HI: 105 pg/ml (77–140), and 72 h post-HI: 380 pg/ml (202–552). The increase in NfL after HI was statistically significant (p < 0.0001, mixed-effects ANOVA). Median NfL levels in sham animals were 41.4 pg/ml at baseline and 92.4 pg/ml at 72 h (p = 0.11, paired t-test). Neither sex, nor treatment with RIPC influenced NfL levels. Weight had a small, not biologically important, influence. NfL levels at 72 h were moderately correlated with histologic brain injury and brain Lac/NAA ratios. NfL 72 h post-HI > 330 pg/ml had a sensitivity of 89% (95% CI, 57%–99%) and a specificity of 52% (95% CI, 34%–69%) for predicting basal ganglia Lac/NAA ratio in the highest quartile. NfL 72 h post-HI > 445 pg/ml had a sensitivity of 90% (95% CI, 60%–99%) and a specificity of 74% (95% CI, 58%–86%) for predicting cortical brain histopathology injury in the highest quartile.ConclusionNfL increased after HI, with the largest values at 72 h post-HI. Early NfL was sensitive but not very specific, whereas NfL at 72 h was both highly sensitive and specific for exposure to moderate-severe HI in this model of HI-induced brain injury. This was supported by a moderate correlation of NfL at 72 h with brain Lac/NAA ratio and histopathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model

et al. 2023

View full text Add to dashboard Cite

show abstract

“… 8 11 28 29 30 31 However, with conflicting findings showing effect and lack of effect, it is still uncertain whether RIPC may induce neuroprotection. 7 Therefore, we aimed to further investigate plausible effects of RIPC by cerebral immunohistochemical markers related to edema, apoptosis, and angiogenesis. However, we found no differences in the brain expression of AQP4, caspase-3, Bcl-2, or VEGF when comparing piglets subjected to HI treated with and without RIPC.…”

Section: Discussionmentioning

confidence: 99%

“…However, the neuroprotective effect of RIPC in neonatal HIE remains questionable. 7 We have previously shown that RIPC of four cycles with five-minutes ischemia and reperfusion was associated with improved brain metabolism in newborn piglets following HI, indicated by a lower brain lactate/Nacetyl-aspartate ratio assessed by magnetic resonance spectroscopy. 8 Brain lactate/N-acetyl-aspartate has been shown to be the most accurate predictor of long-term outcome in neonatal HIE.…”

Section: Accepted Manuscriptmentioning

confidence: 93%

See 1 more Smart Citation

No Differences in Cerebral Immunohistochemical Markers following Remote Ischemic Postconditioning in Newborn Piglets with Hypoxia–Ischemia

Andersen

Bennedsgaard

et al. 2022

Neuropediatrics

Self Cite

View full text Add to dashboard Cite

Background: Despite therapeutic hypothermia, neonates with hypoxic-ischemic encephalopathy still develop neurological disabilities. We have previously investigated neuroprotection by remote ischemic postconditioning (RIPC) in newborn piglets following hypoxia-ischemia (HI). The aim of this study was to further investigate potential effects of RIPC on cerebral immunohistochemical markers related to edema, apoptosis, and angiogenesis. Methods: Brain expression of aquaporin 4, caspase-3, B-cell lymphoma 2, and vascular endothelial growth factor was analyzed by immunohistochemistry in 23 piglets, randomly selected from a larger study of RIPC after HI. Twenty animals were subjected to 45-minutes HI and randomized to treatment with and without RIPC, while three animals were randomized to sham procedures. RIPC was conducted by four conditioning cycles of five-minutes ischemia and reperfusion. Piglets were euthanized 72 hours after the HI insult. Results: Piglets subjected to HI treated with and without RIPC were similar at baseline and following the HI insult. However, piglets randomized to HI alone had longer duration of low blood pressure during the insult. We found no differences in the brain expression of the immunohistochemical markers in any regions of interest or the whole brain between the two HI groups. Conclusions: RIPC did not influence brain expression of markers related to edema, apoptosis, or angiogenesis in newborn piglets at 72 hours after HI. These results support previous findings of limited neuroprotective effect by this RIPC protocol. Our results may have been affected by the time of assessment, use of fentanyl as anesthetic, or limitations related to our immunohistochemical methods.

show abstract

“…Another HI piglet study has also found that RIPC of 10 min ischemia and reperfusion improved brain Lac/NAA ratio and histological cell death; but only in the white matter ( 7 ). A recent review highlighted the need for further studies with focus on the potentially neuroprotective mechanism of RIPC and application of clinically relevant biomarkers for the bridging of results from animal to human studies ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Remote ischemic postconditioning increased cerebral blood flow and oxygenation assessed by magnetic resonance imaging in newborn piglets after hypoxia-ischemia

Kerrn-Jespersen

Andersen²,

Bennedsgaard³

et al. 2022

Front. Pediatr.

View full text Add to dashboard Cite

BackgroundWe have previously investigated neurological outcomes following remote ischemic postconditioning (RIPC) in a newborn piglet model of hypoxic-ischemic encephalopathy. The aim of this study was to further investigate potential mechanisms of neuroprotection by comparing newborn piglets subjected to global hypoxia-ischemia (HI) treated with and without RIPC with regards to measures of cerebral blood flow and oxygenation assessed by functional magnetic resonance imaging.Materials and methodsA total of 50 piglets were subjected to 45 min global HI and randomized to either no treatment or RIPC treatment. Magnetic resonance imaging was performed 72 h after the HI insult with perfusion-weighted (arterial spin labeling, ASL) and oxygenation-weighted (blood-oxygen-level-dependent, BOLD) sequences in the whole brain, basal ganglia, thalamus, and cortex. Four sham animals received anesthesia and mechanical ventilation only.ResultsPiglets treated with RIPC had higher measures of cerebral blood flow in all regions of interest and the whole brain (mean difference: 2.6 ml/100 g/min, 95% CI: 0.1; 5.2) compared with the untreated controls. They also had higher BOLD values in the basal ganglia and the whole brain (mean difference: 4.2 T2*, 95% CI: 0.4; 7.9). Measures were similar between piglets treated with RIPC and sham animals.ConclusionPiglets treated with RIPC had higher measures of cerebral blood flow and oxygenation assessed by magnetic resonance imaging in the whole brain and several regions of interest compared with untreated controls 72 h after the HI insult. Whether this reflects a potential neuroprotective mechanism of RIPC requires further study.

show abstract

Remote ischemic postconditioning for neuroprotection after newborn hypoxia–ischemia: systematic review of preclinical studies

Cited by 5 publications

References 30 publications

Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model

Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model

No Differences in Cerebral Immunohistochemical Markers following Remote Ischemic Postconditioning in Newborn Piglets with Hypoxia–Ischemia

Remote ischemic postconditioning increased cerebral blood flow and oxygenation assessed by magnetic resonance imaging in newborn piglets after hypoxia-ischemia

Contact Info

Product

Resources

About