Brain vascular alterations during the postnatal period in a rat model of intrauterine growth restriction

Abstract

Introduction: Spontaneously hypertensive rats (SHR) endure pregnancy with placental insufficiency, resulting in chronic fetal hypoxia and postnatal neurodevelopmental delay. SHR pups have been proposed as a model for intrauterine growth restriction (IUGR). Impaired cerebrovascular development is strongly related to alterations in the neurovascular unit (NVU). Caveolin-1 (CAV-1) is associated with microvessels, astrocytes and pericytes, the main components of the NVU and it is associated with the tissue response to hypoxic injuries. Objectives: To evaluate brain vascular development during the postnatal period in SHR pups.Methods: SHR and Wistar Kyoto (WKY) pups at P7 and P14 were used to obtain cerebral cortex and cerebellum histological slices. Masson?s trichrome (MT) was performed to detect arterioles; and CAV-1 / IB4 double fluorescent-staining for NVU. We used Image J and AngioTool software to determine the following variables: total number of junctions (TNJ), total number of endpoints(TNEp), vessels area (VA), average vessels length (AVL), lacunarity index (LAC) and ratios IB4/CAV-1. Unpaired Student t-test used for Statistical analysis, the results were reported as Mean ± SEM. Results: Cerebral cortex and cerebellum from SHR P14 presented a significant increase in the number of arterioles. WKY cortex from P7 to P14 manifested a significant increase in TNJ, TNE, andVA; and a decrease in LAC. Only TNE and VPA increased significantly in SHR from P7 to P14. In SHR cortex P14, TVL, and TNEp there were significant differences between ratio CAV-1/IB4, where IB4 had higher expression. In LAC, the situation was reversed. Cerebellum P7 and P14, there were no significant differences in CAV-1 and IB4.Conclusions: The microvascular development of the SHR brain was characterized by an increased number of arterioles, high lacunarity index and poor capillary network. These data together with the altered CAV-1/IB4 ratio suggest a probable delay in NVU consolidation.