In mice and humans, brain microvascular contractility matures postnatally

Abstract

Although great efforts to characterize the embryonic phase of brain microvascular system development have been made, its postnatal maturation has barely been described. Here, we compared the molecular and functional properties of brain vascular cells on postnatal day (P)5 vs. P15, via a transcriptomic analysis of purified mouse cortical microvessels (MVs) and the identification of vascular-cell-type-specific orpreferentially expressed transcripts. We found that endothelial cells (EC), vascular smooth muscle cells (VSMC) and fibroblasts (FB) follow specific molecular maturation programs over this time period.Focusing on VSMCs, we showed that arteriolar VSMC network expands and becomes contractile resulting in a greater cerebral blood flow (CBF), with heterogenous developmental trajectories within cortical regions. Samples of human brain cortex showed the same postnatal maturation process. Thus, the postnatal phase is a critical period during which arteriolar VSMC contractility required for vessel tone and brain perfusion is acquired and mature.

Dynamic local mRNA localization and translation occurs during the postnatal molecular maturation of perivascular astrocytic processes

“…We next sought to determine which mRNAs were localized to PvAPs during postnatal development. We recently described the transcriptome of mechanically purified dorsal cortex MVs on P5 and P15 (Slaoui et al, 2023) (Figure 3a). Since PvAPs stay attached to mechanically purified MVs, we leveraged our knowledge of this transcriptome to detect changes over time in MV's mRNAs that are selectively or specifically expressed in astrocytes (and thus potentially present in PvAPs), according to recently published single‐cell RNA sequencing (RNASeq) datasets for adult brain vascular cells (He et al, 2016; Vanlandewijck et al, 2018).…”

“…RNASeq data were analyzed as described previously (Slaoui et al, 2023). The RNASeq gene expression data and the raw fastq files are available on the GEO repository (http://www.ncbi.nlm.nih.gov/geo/), with the accession number GSE173844.…”

“…(a) Flowchart for the identification of mRNAs selectively or specifically expressed in astrocytes and present in PvAPs. These transcripts were identified in previously published single-cell RNAseq datasets (He et al, 2016;Vanlandewijck et al, 2018) (RNAseq data are also presented in Table S1) and compared with a previous transcriptional analysis of MVs extracted from the dorsal cortex on P5 and P15 (Slaoui et al, 2023). In the purified MVs, PvAPs (in green) remain attached to the vessel surface, which allows the identification of mRNAs selectively or specifically expressed in astrocytes and present in cortical PvAPs on Mlc1, Kcnj10, Slc1a2, Ntsr2 and Aqp4) or downregulated (Fabp7, Ptprz1…”

“…Recent research results suggest that all cortical astrocytes have PvAPs and contact between 1 and 3 vessels (Hosli et al, 2022). The gliovascular unit develops after birth and requires the densification of the vascular network (Coelho‐Santos et al, 2021; Coelho‐Santos & Shih, 2020), the maturation of vascular smooth muscle cell contractility (Slaoui et al, 2023), the recruitment of perivascular macrophages (Karam et al, 2022) and fibroblasts (Jones et al, 2023), and the production and maturation of astrocytes and PvAPs. In the cortex, astrocytogenesis starts at around the time of birth and peaks during the following week.…”

Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?

“…The maturation of the brain primary vascular network involves the recruitment of mural cells (VSMCs and pericytes), establishment of the BBB properties (barriergenesis), the generation of the extracellular matrix, and enwrapping by astrocytic endfeet. Cerebral arteries undergo refinement until the third postnatal month [[40]] as studies have shown that arteriolar VSMC expands and matures during this period and becomes contractile to better control cerebral blood flow [[41]]. Astrocytic recruitment and differentiation occurs during the late embryonic and early postnatal periods [[42]].…”