Yates Nathanael J, Feindel Kirk W, Mehnert Andrew, Beare Richard, Quick Sophia, Blache Dominique, Pillow J Jane, Hunt Rod W
School of Human Sciences, University of Western Australia, Perth 6009, Australia.
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia.
Brain Sci. 2020 Apr 3;10(4):211. doi: 10.3390/brainsci10040211.
Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological safety profile of postnatal dexamethasone in preterm lambs. Lambs were delivered via caesarean section at 129 days' (d) gestation (full term ≈ 150 d) with saline-vehicle control (Saline, = 9), low-dose tapered dexamethasone (cumulative dose = 0.75 mg/kg, = 8), or high-dose tapered dexamethasone (cumulative dose = 2.67 mg/kg, = 8), for seven days. Naïve fetal lambs (136 d gestation) were used as end-point maturation controls. The left-brain hemispheres were immersion-fixed in 10 % formalin (24 h), followed by paraformaldehyde (>6 months). Image sequences were empirically optimized for T1- and T2-weighted MRI and analysed using accessible methods. Spontaneous lesions detected in the white matter of the frontal cortex, temporo-parietal cortex, occipital lobe, and deep to the parahippocampal gyrus were confirmed with histology. Neither postnatal dexamethasone treatment nor gestation showed any associations with lesion incidence, frontal cortex (total, white, or grey matter) or hippocampal volume (all > 0.05). Postnatal dexamethasone did not appear to adversely affect neurodevelopment. Our post-mortem MRI analysis pipeline is suitable for other animal models of brain development.
产后使用的糖皮质激素如地塞米松可有效促进早产儿肺部发育，但由于担心其对神经系统的损害，使用时需谨慎。我们开发了一种用于尸检磁共振成像（MRI）的分析流程，以评估脑发育情况，从而了解产后地塞米松对早产羔羊神经系统的安全性。妊娠129天（足月约150天）时通过剖宫产分娩羔羊，分为生理盐水对照（生理盐水组，n = 9）、低剂量递减地塞米松组（累积剂量 = 0.75 mg/kg，n = 8）或高剂量递减地塞米松组（累积剂量 = 2.67 mg/kg，n = 8），给药7天。未经处理的胎羊（妊娠136天）用作终点成熟对照。将左侧脑半球浸入10%福尔马林中固定24小时，然后再用多聚甲醛固定超过6个月。通过经验优化T1加权和T2加权MRI的图像序列，并使用可及的方法进行分析。在额叶皮质、颞顶叶皮质、枕叶白质以及海马旁回深部检测到的自发性病变通过组织学得到证实。产后地塞米松治疗和妊娠与病变发生率、额叶皮质（全脑、白质或灰质）或海马体积均无关联（所有P>0.05）。产后地塞米松似乎并未对神经发育产生不利影响。我们的尸检MRI分析流程适用于其他脑发育动物模型。
