β-Estradiol 17-acetate enhances the in vitro vitality of endothelial cells isolated from the brain of patients subjected to neurosurgery

In the current landscape of endothelial cell isolation for building in vitro models of the blood-brain barrier,our work moves towards reproducing the features of the neurovascular unit to achieve glial compliance through an innovative biomimetic coating technology for brain chronic implants.We hypothesized that the autologous origin of human brain mic rovascular endothelial cells(hBMECs)is the first requirement for the suitable coating to prevent the glial inflammato ry response trigge red by foreign neuroprosthetics.Therefo re,this study established a new procedure to preserve the in vitro viability of hBMECs isolated from gray and white matter specimens taken from neurosurge ry patients.Culturing adult hBMECs is generally considered a challenging task due to the difficult survival ex vivo and progressive reduction in proliferation of these cells.The addition of 10 nMβ-estradiol 17-acetate to the hBMEC culture medium was found to be an essential and discriminating factor promoting adhesion and proliferation both after isolation and thawing,suppo rting the well-known protective role played by estrogens on microvessels.In particular,β-estradiol 17-acetate was critical for both freshly isolated and thawed female-derived hBMECs,while it was not necessary for freshly isolated male-derived hBMECs;however,it did countera ct the decay in the viability of the latter after thawing.The tumo r-free hBMECs were thus cultured for up to 2 months and their growth efficiency was assessed befo re and after two periods of cryopreservation.Des pite the thermal stress,the hBMECs remained viable and suitable for re-freezing and storage for several months.This approach increasing in vitro viability of hBMECs opens new perspectives for the use of cryopreserved autologous hBMECs as biomimetic therapeutic tools,offering the potential to avoid additional surgical sampling for each patient.

BACE1 role in Alzheimer’s disease and other dementias:from the theory to the practice

Beta-site amyloid precursor protein(APP)cleaving enzyme-1(BACE1):brief overview on the biology and its role in Alzheimer’s disease(AD)pathogenesis:AD is a multifactorial and multifaceted disease,with a complex and still not completely understood pathogenesis(Cervellati et al.,2016;Iturria-Medina et al.,2016).Multiple hypotheses have been proposed to explain the pathobiology of the disease.

OxInflammation in Alzheimer's disease

Oxlnflammation:definition and role in disease:Oxlnflammation has been introduced as a new term in the biomedical field to highlight the deep and mutual relationship between the dysregulation of redox and immune homeostasis(Valacchi et al.,2018).Regardless of which is the initial spark,inflammation cannot take place without a concomitant oxidative stress response and vice-versa.In other words,they are sides of the same coin.