Table 2 Studies investigating the effects of treatments on the NVU in FGR.
Authors | Experimental model | Intervention trialled | Key findings |
|---|---|---|---|
Castillo-Melendez et al. (2017)44 | Lambs delivered naturally at term (~147 days) and euthanised 24 h later FGR induced via SUAL at ~105 days gestation | Antenatal treatment with either saline (placebo) or Melatonin infusion (0.1 mg/kg) started 4 h after SUAL surgery | No significant difference in blood vessel density and proliferation (VEGF expression) between FGR group and intervention group Improved endothelial cell proliferation (Glut1 expression) with melatonin intervention Normalisation of pericyte and astrocyte end-feet coverage with melatonin intervention Albumin extravasation and microhaemorrhage prevention in the treatment group |
Chand et al. (2021)49 | Term FGR piglets (<10th percentile birth weight) and NG piglets (10–90th) percentile Euthanasia on postnatal day 4 | cECFC/MSC/sham treatment administered on postnatal day 1 | cECFC treatment increased vessel density while MSC had no effect cECFC treatment restored total vascular length as well as partially improved vessel branching cECFC reduced incidences of albumin and IgG-labelled area cECFC increased GFAP-positive vessel coverage cECFC microglial morphology similar to NG cECFC decreased glial activation and increased modulation of inflammatory mediators cECFC reduces neuronal apoptosis in the brain |
Chand et al. (2022)48 | FGR piglets (<10th percentile birth weight) and NG piglets (10–90th percentile) Euthanasia on postnatal day 4 | Liquid ibuprofen was given via an oral dose of 20 mg/kg/day on postnatal day 1 and 10 mg/kg/day on days 2 and 3 | Intervention group displayed juxtavascular astrocyte and microglia resting morphology similar to that observed in NG group Ibuprofen reduced the frequency of hypertrophic astrocyte end-feet and normalised vessel coverage Ibuprofen reduced the number of activated juxtavascular microglia Ibuprofen reduced pro-inflammatory cytokines and increased anti-inflammatory mediator Albumin and IgG extravasation reduced in ibuprofen treatment compared to untreated FGR Increased apoptosis in FGR ameliorated following ibuprofen treatment Decreased ZO-1 vessel coverage not recovered by ibuprofen treatment |
Malhotra et al. (2020)45 | Twin lambs delivered (127 days), intubated and ventilated then euthanised 24 h later FGR induced at 88 days gestation via SUAL in one twin | Allogeneic umbilical cord blood mononuclear cells (25 million/kg) were suspended in 2–3 ml of sterile saline and given intravenously (via the umbilical vein) to preterm ventilated lambs at 1 h of life | UCBC therapy reduced the number of activated microglial cells UCBC therapy resulted in significantly more increased endothelial cell coverage compared to FGR UCBC therapy normalised co-localisation of pericyte coverage UCBC therapy decreased albumin extravasation into the brain parenchyma |
Bell et al. (2023)113 | Preterm lambs studied at 127 days gestation FGR induced via SUAL at ~88 days gestation | 1 × 107 ECFCs delivered intravenously to fetal lambs in utero at 113 days gestation | ECFC administration increased both vessel sizes and overall vascular density throughout grey and white matter regions of both AGA and FGR lambs ECFC administration increased vascular astrocyte coverage in the cortical grey matter and subcortical white matter of both AGA and FGR lambs ECFC administration increased VEGF expression in the cortical grey matter and subcortical white matter of both AGA and FGR lambs ECFC administration produced no significant difference in vascular pericyte coverage in the brains of either AGA or FGR lambs ECFC administration produced no significant difference in vascular GLUT1 expression in the brains of either AGA or FGR lambs |
