Chronic inflammation and impaired development of the preterm brain

Bennet, Laura; Dhillon, Simerdeep K; Lear, Christopher A.; Heuij, Lotte Van Den; King, Victoria J; Dean, Justin M.; Wassink, Guido; Davidson, J.; Gunn, Alistair J.

doi:10.1016/j.jri.2017.11.003

Cited by 64 publications

(62 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…; Bennet et al . ). Key neuroprotection strategies in this phase include treating chronic inflammation and stimulation of endogenous factors which support proliferation, migration and maturation of glia and neurons (Hagberg et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

“…; Bennet et al . ). Treatments such as stem cell therapy have utility in this phase, given their multimodal effects in reducing inflammation and promoting release of trophic factors (Fleiss et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

“…; Bennet et al . ). Further, there is a clear role for postnatal neurorehabilitation for optimising development of the neural network (Pitcher et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

“…; Bennet et al . ). Inflammation of chorionic and amniotic membranes (chorioamnionitis), for example, is reported in nearly 95% of preterm births at 21–24 weeks of gestation, and in about 10% of deliveries at 33–36 weeks (Kim et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

“…; Bennet et al . ), but there is also chronic inflammation and epigenetic changes lasting for weeks to months after injury that may prevent optimal neurorepair (Fleiss & Gressens, ; Galinsky et al . ; Bennet et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 99%

See 4 more Smart Citations

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Dhillon

Lear

Galinsky

et al. 2018

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Brain injury around birth is associated with nearly half of all cases of cerebral palsy. Although brain injury is multifactorial, particularly after preterm birth, acute hypoxia-ischaemia is a major contributor to injury. It is now well established that the severity of injury after hypoxia-ischaemia is determined by a dynamic balance between injurious and protective processes. In addition, mothers who are at risk of premature delivery have high rates of diabetes and antepartum infection/inflammation and are almost universally given treatments such as antenatal glucocorticoids and magnesium sulphate to reduce the risk of death and complications after preterm birth. We review evidence that these common factors affect responses to fetal asphyxia, often in unexpected ways. For example, glucocorticoid exposure dramatically increases delayed cell loss after acute hypoxia-ischaemia, largely through secondary hyperglycaemia. This critical new information is important to understand the effects of clinical treatments of women whose fetuses are at risk of perinatal asphyxia.

show abstract

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

“…; Bennet et al . ). Further, there is a clear role for postnatal neurorehabilitation for optimising development of the neural network (Pitcher et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 99%

See 3 more Smart Citations

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Dhillon

Lear

Galinsky

et al. 2018

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

Intranasal mesenchymal stem cell therapy to boost myelination after encephalopathy of prematurity

Vaes

Kammen

Trayford

et al. 2020

Glia

View full text Add to dashboard Cite

Encephalopathy of prematurity (EoP) is a common cause of long‐term neurodevelopmental morbidity in extreme preterm infants. Diffuse white matter injury (dWMI) is currently the most commonly observed form of EoP. Impaired maturation of oligodendrocytes (OLs) is the main underlying pathophysiological mechanism. No therapies are currently available to combat dWMI. Intranasal application of mesenchymal stem cells (MSCs) is a promising therapeutic option to boost neuroregeneration after injury. Here, we developed a double‐hit dWMI mouse model and investigated the therapeutic potential of intranasal MSC therapy. Postnatal systemic inflammation and hypoxia‐ischemia led to transient deficits in cortical myelination and OL maturation, functional deficits and neuroinflammation. Intranasal MSCs migrated dispersedly into the injured brain and potently improved myelination and functional outcome, dampened cerebral inflammationand rescued OL maturation after dWMI. Cocultures of MSCs with primary microglia or OLs show that MSCs secrete factors that directly promote OL maturation and dampen neuroinflammation. We show that MSCs adapt their secretome after ex vivo exposure to dWMI milieu and identified several factors including IGF1, EGF, LIF, and IL11 that potently boost OL maturation. Additionally, we showed that MSC‐treated dWMI brains express different levels of these beneficial secreted factors. In conclusion, the combination of postnatal systemic inflammation and hypoxia‐ischemia leads to a pattern of developmental brain abnormalities that mimics the clinical situation. Intranasal delivery of MSCs, that secrete several beneficial factors in situ, is a promising strategy to restore myelination after dWMI and subsequently improve the neurodevelopmental outcome of extreme preterm infants in the future.

show abstract

Umbilical cord blood cells for the treatment of preterm white matter injury: Potential effects and treatment options

Qiu

Qian

et al. 2020

J of Neuroscience Research

View full text Add to dashboard Cite

Preterm birth is a global public health problem. A large number of preterm infants survive with preterm white matter injury (PWMI), which leads to neurological deficits, and has multifaceted etiology, clinical course, monitoring, and outcomes. The principal upstream insults leading to PWMI initiation are hypoxia‐ischemia and infection and/or inflammation and the key target cells are late oligodendrocyte precursor cells. Current PWMI treatments are mainly supportive, and thus have little effect in terms of protecting the immature brain or repairing injury to improve long‐term outcomes. Umbilical cord blood (UCB) cells comprise abundant immunomodulatory and stem cells, which have the potential to reduce brain injury, mainly due to anti‐inflammatory and immunomodulatory mechanisms, and also through their release of neurotrophic or growth factors to promote endogenous neurogenesis. In this review, we briefly summarize PWMI pathogenesis and pathophysiology, and the specific properties of different cell types in UCB. We further explore the potential mechanism by which UCB can be used to treat PWMI, and discuss the advantages of and potential issues related to UCB cell therapy. Finally, we suggest potential future studies of UCB cell therapy in preterm infants.

show abstract

Chronic inflammation and impaired development of the preterm brain

Cited by 64 publications

References 177 publications

The fetus at the tipping point: modifying the outcome of fetal asphyxia

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Intranasal mesenchymal stem cell therapy to boost myelination after encephalopathy of prematurity

Umbilical cord blood cells for the treatment of preterm white matter injury: Potential effects and treatment options

Contact Info

Product

Resources

About