Dihydrolipoic Acid–Gold Nanoclusters Regulate Microglial Polarization and Have the Potential To Alter Neurogenesis

Abstract

Microglia-mediated neuroinflammation is one of the most significant features in a variety of central nervous system (CNS) disorders such as traumatic brain injury, stroke, and many neurodegenerative diseases. Microglia become polarized upon stimulation. The two extremes of the polarization are the neuron-destructive proinflammatory M1-like and the neuron-regenerative M2-like phenotypes. Thus, manipulating microglial polarization toward the M2 phenotype is a promising therapeutic approach for CNS repair and regeneration. It has been reported that nanoparticles are potential tools for regulating microglial polarization. Gold nanoclusters (AuNCs) could penetrate the blood–brain barrier and have neuroprotective effects, suggesting the possibility of utilizing AuNCs to regulate microglial polarization and improve neuronal regeneration in CNS. In the current study, AuNCs functionalized with dihydrolipoic acid (DHLA–AuNCs), an antioxidant with demonstrated neuroprotective roles, were prepared, and their effects on polarization of a microglial cell line (BV2) were examined. DHLA–AuNCs effectively suppressed proinflammatory processes in BV2 cells by inducing polarization toward the M2-like phenotype. This was associated with a decrease in reactive oxygen species and reduced NF-kB signaling and an improvement in cell survival coupled with enhanced autophagy and inhibited apoptosis. Conditioned medium from DHLA–AuNC-treated BV2 cells was able to enhance neurogenesis in both the neuronal cell line N2a and in an ex vivo brain slice stroke model. The direct treatment of brain slices with DHLA–AuNCs also ameliorated stroke-related tissue injury and reduced astrocyte activation (astrogliosis). This study suggests that by regulating neuroinflammation to improve neuronal regeneration, DHLA–AuNCs could be a potential therapeutic agent in CNS disorders.

Association between Heavy Metals and Rare Earth Elements with Acute Ischemic Stroke: A Case-Control Study Conducted in the Canary Islands (Spain)

“…In the present study, blood concentration of gold was significantly higher among controls (Table 4) and the association with stroke was also found in multivariate analysis (Table 3). Although the frequency of detection of gold did not meet the quality standards imposed to guarantee a minimum statistical power, the present result agrees with others which suggest that gold is an interesting factor to consider for the treatment of stroke [46]. The neuroprotective role of cerium has been previously reported [47,48].…”

“…The role of these minority elements seems to be more important than initially thought. Thus, it has been recently published that gold nanoclusters penetrate the blood−brain barrier and have neuroprotective effects, suggesting the possibility of utilizing this nanoparticles to regulate microglial polarization and improve neuronal regeneration in central nervous system [46]. In the present study, blood concentration of gold was significantly higher among controls (Table 4) and the association with stroke was also found in multivariate analysis (Table 3).…”

Stimulator of IFN genes mediates neuroinflammatory injury by suppressing AMPK signal in experimental subarachnoid hemorrhage

“…M1 microglia, which are usually activated by immune receptors including toll-like receptors (TLRs), and nucleotide-binding oligomerization domains (NODs), can recognize and respond to pathogens by secreting proinflammatory cytokines and chemokines (such as IL-1β and TNFα), ultimately elevating the immune response and exacerbating brain damage [9,10]. In contrast to the proinflammatory M1 phenotype, M2 microglia have been proved to mediate neuroprotective effects via producing anti-inflammatory cytokines such as IL-10 and promoting tissue repair and angiogenesis [11,12]. Evidence above suggests that suppressing prolonged neuroinflammation via inhibiting the M1 phenotype and/or promoting the M2 phenotype might be an effective and promising therapeutic strategy for SAH as well.…”

Inhibited CSF1R Alleviates Ischemia Injury via Inhibition of Microglia M1 Polarization and NLRP3 Pathway

“…Overexpression of S100B which is expressed in microglia could aggravate cerebral ischemia through activating NF- κ B expression and inhibiting M2 stimuli expression to promote microglia M1 polarization [ 26 ]. Inhibited microglia M1 and activated M2 polarization by treating with curcumin and dihydrolipoic acid-gold nanoclusters prevents ischemic stroke and has the potency to ameliorate neurogenesis [ 27 ]. In this study, the expression of TNF- α and iNOS mRNA induced by focal cerebral ischemic injury was increased significantly, and the number of microglial cells at the injured site increased as well.…”