No abstract

Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm 2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.

Recently, accumulating evidence has highlighted the role of endothelial dysfunction in COVID‐19 progression. Coronary microvascular dysfunction (CMD) plays a pivotal role in cardiovascular disease (CVD) and CVD‐related risk factors (eg, age, gender, hypertension, diabetes mellitus, and obesity). Equally, these are also risk factors for COVID‐19. The purpose of this review was to explore CMD pathophysiology in COVID‐19, based on recent evidence. COVID‐19 mechanisms were reviewed in terms of imbalanced renin‐angiotensin‐aldosterone‐systems (RAAS), systemic inflammation and immune responses, endothelial dysfunction, and coagulatory disorders. Based on these mechanisms, we addressed CMD pathophysiology within the context of COVID‐19, from five perspectives. The first was the disarrangement of local RAAS and Kallikrein‐kinin‐systems attributable to SARS‐Cov‐2 entry, and the concomitant decrease in coronary microvascular endothelial angiotensin I converting enzyme 2 (ACE2) levels. The second was related to coronary microvascular obstruction, induced by COVID‐19‐associated systemic hyper‐inflammation and pro‐thrombotic state. The third was focused on how pneumonia/acute respiratory distress syndrome (ARDS)‐related systemic hypoxia elicited oxidative stress in coronary microvessels and cardiac sympathetic nerve activation. Fourthly, we discussed how autonomic nerve dysfunction mediated by COVID‐19‐associated mental, physical, or physiological factors could elicit changes in coronary blood flow, resulting in CMD in COVID‐19 patients. Finally, we analyzed reciprocity between the coronary microvascular endothelium and perivascular cellular structures due to viremia, SARS‐CoV‐2 dissemination, and systemic inflammation. These mechanisms may function either consecutively or intermittently, finally culminating in CMD‐mediated cardiovascular symptoms in COVID‐19 patients. However, the underlying molecular pathogenesis remains to be clarified.

We discuss the role of Salvianolic acid A(SAA), one of the main effective components in Salvia Miltiorrhiza (known as 'Danshen' in traditional Chinese medicine), in apoptotic factors, the production of oxidative products, and the expression of Akt and NF-κB in angiotensin II (Ang II)-mediated murine macrophages. In the present study, Ang II was added to mice abdominal macrophages with or without addition of SAA. After cell identification, apoptosis was measured by DNA strand break level with TdT-mediated dUTP nick-end labeling (TUNEL) staining, and the expression of Bcl-2 and Bax. Intracellular concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Western blotting determined the expression of Akt, p-Akt, NF-κB and p-NF-κB. Ly294002 (the inhibitor of PI3K) was used to determine the mechanism of SAA. Ang II (1 µM) significantly increased the number of TUNEL-positive cells and Bax expression, but reduced Bcl-2 expression. These effects were antagonized when the cells were pretreated with SAA. SAA decreased MDA, but increased SOD in the cell lysis solution treated with Ang II. It markedly reduced the level of p-NF-κB, as also p-Akt, which was partly blocked by Ly294002. SAA prevents Ang IIinduced apoptosis, oxidative stress and related protein expression in the macrophages. It also inhibits the activation of Akt.