Intrauterine growth restriction disrupts the postnatal critical period of synaptic plasticity in the mouse dorsal hippocampus in a model of hypertensive disease of pregnancy

Introduction: Intrauterine growth restriction (IUGR) from hypertensive disease of pregnancy complicates up to 10% of all pregnancies. Significant hippocampal-dependent cognitive and memory impairments as well as neuropsychiatric disorders have been linked to IUGR. Because disturbance of hippocampal critical period (CPd) of synaptic plasticity leads to impairments similar to those described in IUGR human offspring, we hypothesized that IUGR would perturb the CPd of synaptic plasticity in the mouse hippocampus in our model. Methods: IUGR was produced by a micro-osmotic pump infusion of the potent vasoconstrictor U-46619, a thromboxane A2-agonist (TXA2), at embryonic day (E) 12.5 in C57BL/6J mouse dams to precipitate hypertensive disease of pregnancy and IUGR. Sham-operated mice acted as controls. At P10, P18, and P40, we assessed astrogliosis using GFAP-IHC. In dorsal CA1 and CA3 subfields, we assessed the immunoreactivities (IR) (IF-IHC) to: i) parvalbumin (PV) and glutamate decarboxylase (GAD) 65/67, involved in CPd onset; ii) PSA-NCAM, that antagonizes CPd onset; iii) NPTX2, necessary for excitatory synapse formation and engagement of CPd; and iv) MBP and WFA, staining perineural nets (PNNs), marking CPd closure. ImageJ/Fiji and IMARIS were used for image processing and SPSS v24 for statistical analysis. Results: Although PV+ interneuron (IN) numbers and IR intensity were unchanged, development of GAD65/67+ synaptic boutons was accelerated at P18 IUGR mice, and inversely correlated with decreased expression of PSA-NCAM in the CA of P18 IUGR mice at P18. NPTX2 + puncta and total volume were persistently decreased in the CA3 pyramidal and radiatum layers of IUGR mice from P18 to P40. At P40, axonal myelination (MBP+) in CA3 of IUGR mice was decreased and correlated with NPTX2 deficits. Lastly, the volume and integrity of the PNNs in the dorsal CA was disrupted in IUGR mice at P40. Discussion/Conclusion: IUGR disrupts the molecular and structural initiation, consolidation and closure of the CPd of synaptic plasticity in the mouse hippocampus in our model, which may explain the learning and memory deficits observed in juvenile IUGR mice and the cognitive disorders seen in human IUGR offspring. The mechanistic links warrant further investigation, to identify therapeutic targets to prevent neurodevelopmental deficits in patients affected by IUGR.

Identification of a High-Risk Group of New-Onset Cardiovascular Disease in Occupational Drivers by Analyzing Heart Rate Variability

Purpose: This cohort study evaluated the effectiveness of noninvasive heart rate variability (HRV) analysis to assess the risk of cardiovascular disease over a period of 8 years. Methods: Personal and working characteristics were collected before biochemistry examinations and 5 min HRV tests from the Taiwan Bus Driver Cohort Study (TBDCS) in 2005. This study eventually identified 161 drivers with cardiovascular disease (CVD) and 627 without between 2005 and 2012. Estimation of the hazard ratio was analyzed by using the Cox proportional-hazards model. Results: Subjects with CVD had an overall lower standard deviation of NN intervals (SDNN) than their counterparts did. The SDNN index had a strong association with CVD, even after adjusting for risk factors. Using a median split for SDNN, the hazard ratio of CVD was 1.83 (95% CI = 1.10–3.04) in Model 1 and 1.87 (95% CI = 1.11–3.13) in Model 2. Furthermore, the low-frequency (LF) index was associated with a risk of CVD in the continuous approach. For hypertensive disease, the SDNN index was associated with increased risks in both the continuous and dichotomized approaches. When the root-mean-square of the successive differences (RMSSDs), high frequency (HF), and LF were continuous variables, significant associations with hypertensive disease were observed. Conclusions: This cohort study suggests that SDNN and LF levels are useful for predicting 8 year CVD risk, especially for hypertensive disease. Further research is required to determine preventive measures for modifying HRV dysfunction, as well as to investigate whether these interventions could decrease CVD risk among professional drivers.

Oxygen deficiency in hypertension

The book is intended for a wide range of practitioners. The description of specific data on oxygen deficiency at various stages of hypertensive disease is preceded by a presentation of general information about the physiology of respiration, its impairments and methods for studying the functional state of the respiratory apparatus