The antipsychotic chlorpromazine reduces neuroinflammation by inhibiting microglial voltage-gated potassium channels.

Neuroinflammation, the result of microglial activation, is associated with the pathogenesis of a wide range of psychiatric and neurological disorders. Recently, chlorpromazine (CPZ), a dopaminergic D2 receptor antagonist and schizophrenia therapy, was proposed to exert antiinflammatory effects in the central nervous system. Here, we report that the expression of Kv1.

Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting.

Amitriptyline (AMI) has been used to treat neuropathic pain. However, the clinical outcomes remain unsatisfactory, presumably due to a limited understanding of the underlying molecular mechanisms. Here, we investigated a drug repositioning strategy using a low-dose of AMI encapsulated in poly (D, L lactic-co-glycolic acid) (PLGA) nanoparticles (AMI NPs) for neuropathic pain, since PLGA nanoparticles are known to enhance delivery to microglia.

Rejuvenating aged microglia by p16-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer's disease.

Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance.

Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury.

Astrocytes are highly activated following brain injuries, and their activation influences neuronal survival. Additionally, SOX9 expression is known to increase in reactive astrocytes. However, the role of SOX9 in activated astrocytes following ischemic brain damage has not been clearly elucidated yet.

Employing the sustained-release properties of poly(lactic-co-glycolic acid) nanoparticles to reveal a novel mechanism of sodium-hydrogen exchanger 1 in neuropathic pain.

Neuropathic pain is caused by injury or disease of the somatosensory system, and its course is usually chronic. Several studies have been dedicated to investigating neuropathic pain-related targets; however, little attention has been paid to the persistent alterations that these targets, some of which may be crucial to the pathophysiology of neuropathic pain. The present study aimed to identify potential targets that may play a crucial role in neuropathic pain and validate their long-term impact.

PINK1 siRNA-loaded poly(lactic-co-glycolic acid) nanoparticles provide neuroprotection in a mouse model of photothrombosis-induced ischemic stroke.

PTEN-induced kinase 1 (PINK1) is a well-known critical marker in the pathway for mitophagy regulation as well as mitochondrial dysfunction. Evidence suggests that mitochondrial dynamics and mitophagy flux play an important role in the development of brain damage from stroke pathogenesis. In this study, we propose a treatment strategy using nanoparticles that can control PINK1.

Oxygenated Water Increases Seizure Threshold in Various Rodent Seizure Models.

Oxygenated water (OW) contains more oxygen than normal drinking water. It may induce oxygen enrichment in the blood and reduce oxidative stress. Hypoxia and oxidative stress could be involved in epilepsy.

Perampanel Reduces Brain Damage via Induction of M2 Microglia in a Neonatal Rat Stroke Model.

Purpose: Ischemic stroke is a leading cause of death and disability worldwide. Additionally, neonatal ischemia is a common cause of neonatal brain injury, resulting in cerebral palsy with subsequent learning disabilities and epilepsy. However, there is currently a lack of effective treatments available for patients with perinatal ischemic stroke.

Targeting spinal microglia with fexofenadine-loaded nanoparticles prolongs pain relief in a rat model of neuropathic pain.

Targeting microglial activation is emerging as a clinically promising drug target for neuropathic pain treatment. Fexofenadine, a histamine receptor 1 antagonist, is a clinical drug for the management of allergic reactions as well as pain and inflammation. However, the effect of fexofenadine on microglial activation and pain behaviors remains elucidated.

p16INK4a-siRNA nanoparticles attenuate cartilage degeneration in osteoarthritis by inhibiting inflammation in fibroblast-like synoviocytes.

In osteoarthritis (OA), chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favoring disease progression. Although senescence biomarker p16INK4a expression is known to induce aging by halting the cell cycle, therapeutic applications for p16INK4a targeting are limited. Here, we aimed to reduce cartilage damage and alleviate pain using p16INK4a nanoparticles in OA.

Application of PLGA nanoparticles to enhance the action of duloxetine on microglia in neuropathic pain.

Duloxetine (DLX) is a selective serotonin and noradrenaline reuptake inhibitor (SNRI) used for the treatment of pain, but it has been reported to show side effects in 10-20% of patients. Its analgesic efficacy in central pain is putatively related to its influence on descending inhibitory neuronal pathways. However, DLX can also affect the activation of microglia.

siRNA-Encapsulated Poly (Lactic--Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB.

Zwitterionic polydopamine coatings suppress silicone implant-induced capsule formation.

A synthetic zwitterionic dopamine derivative (ZW-DOPA) containing both catechol and amine groups was recently shown to exhibit excellent antifouling activity on marine surfaces. Here, we have extended these analyses to investigate the effects of ZW-DOPA coating on silicone implants. Successful formation of ZW-DOPA coatings on silicone implants was confirmed based on a combination of decreased static water contact angles on silicone implants, evidence of new peaks at 400.

Vitamin E reduces spasms caused by prenatal stress by lowering calpain expression.

Background: Prenatal stress increases the susceptibility of infants to seizures and is known to be associated with oxidative stress. Recent studies suggest that vitamin E has beneficial effects in various neurological diseases due to its antioxidant properties. In this study, we investigated the relationship between prenatal stress and vitamin E treatment on N-methyl-D-aspartate (NMDA)-induced spasms.

Protective Effects of ShcA Protein Silencing for Photothrombotic Cerebral Infarction.

Reactive oxygen species (ROS) exacerbate stroke-induced cell damage. We found that ShcA, a protein that regulates ROS, is highly expressed in a Rose Bengal photothrombosis model. We investigated whether ShcA is essential for mitophagy in ROS-induced cellular damage and determined whether ROS exacerbate mitochondrial dysfunction via ShcA protein expression.

TAP2, a peptide antagonist of Toll-like receptor 4, attenuates pain and cartilage degradation in a monoiodoacetate-induced arthritis rat model.

Because inflammation in osteoarthritis (OA) is related to the Toll-like receptor 4 (TLR4) signaling cascades, TLR4 is a reasonable target for developing therapeutics for OA. Thus, we investigated whether TAP2, a peptide antagonist of TLR4, reduces the monoiodoacetate (MIA)-induced arthritic pain and cartilage degradation in rats. TLR4 expression of human OA chondrocytes and synoviocytes and the knee joint tissue of MIA-induced arthritis were evaluated.

Extracorporeal shockwave therapy enhances peripheral nerve remyelination and gait function in a crush model.

Background: Conservative treatment, such as electrical stimulation and steroid injection, have been employed in an attempt to improve symptoms after peripheral nerve injury, without significant success. Although non-invasive and safe extracorporeal shockwave therapy (ESWT) can be a practical alternative, the therapeutic effects of ESWT on peripheral nerve remyelination has not been established.

Objectives: To investigate the effects of ESWT on peripheral nerve remyelination and gait function for 5 weeks in a sciatic nerve crush model.

Preventive Effects of Neuroprotective Agents in a Neonatal Rat of Photothrombotic Stroke Model.

Neonatal ischemic stroke has a higher incidence than childhood stroke. Seizures are the first sign for the need for clinical assessment in neonates, but many questions remain regarding treatments and follow-up modalities. In the absence of a known pathophysiological mechanism, only supportive care is currently provided.

CX3CR1-Targeted PLGA Nanoparticles Reduce Microglia Activation and Pain Behavior in Rats with Spinal Nerve Ligation.

Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats.

p66shc siRNA-Encapsulated PLGA Nanoparticles Ameliorate Neuropathic Pain Following Spinal Nerve Ligation.

p66shc, a member of the shc adaptor protein family, has been shown to participate in regulation of mitochondrial homeostasis, apoptosis, and autophagosome formation. The present study was performed to investigate whether p66shc siRNA-encapsulated poly(d,l-lactic--glycolic acid) nanoparticles (p66shc siRNA-PLGA NPs) can attenuate spinal nerve ligation (SNL)-induced neuropathic pain in rats. The SNL-induced pain behavior was decreased in the p66shc siRNA-PLGA NP-treated group compared with the scrambled siRNA-PLGA NP-treated group.

p66shc siRNA Nanoparticles Ameliorate Chondrocytic Mitochondrial Dysfunction in Osteoarthritis.

Background: Osteoarthritis (OA) is the most common type of joint disease associated with cartilage breakdown. However, the role played by mitochondrial dysfunction in OA remains inadequately understood. Therefore, we investigated the role played by p66shc during oxidative damage and mitochondrial dysfunction in OA and the effects of p66shc downregulation on OA progression.

miRNA 146a-5p-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles impair pain behaviors by inhibiting multiple inflammatory pathways in microglia.

We investigated whether miRNA (miR) 146a-5p-loaded nanoparticles (NPs) can attenuate neuropathic pain behaviors in the rat spinal nerve ligation-induced neuropathic pain model by inhibiting activation of the NF-κB and p38 MAPK pathways in spinal microglia. After NP preparation, miR NPs were assessed for their physical characteristics and then injected intrathecally into the spinal cords of rat spinal nerve ligation rats to test their analgesic effects. miR NPs reduced pain behaviors for 11 days by negatively regulating the inflammatory response in spinal microglia.

p47phox siRNA-Loaded PLGA Nanoparticles Suppress ROS/Oxidative Stress-Induced Chondrocyte Damage in Osteoarthritis.

Osteoarthritis (OA) is the most common joint disorder that has had an increasing prevalence due to the aging of the population. Recent studies have concluded that OA progression is related to oxidative stress and reactive oxygen species (ROS). ROS are produced at low levels in articular chondrocytes, mainly by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and ROS production and oxidative stress have been found to be elevated in patients with OA.

Pink1-Mediated Chondrocytic Mitophagy Contributes to Cartilage Degeneration in Osteoarthritis.

Cartilage loss is a central event in the pathogenesis of osteoarthritis (OA), though other than mechanical loading, the biochemical mechanisms underlying OA pathology remain poorly elucidated. We investigated the role of Pink1-mediated mitophagy in mitochondrial fission, a crucial process in OA pathogenesis. We used a monosodium iodoacetate (MIA)-induced rodent model of OA, which inhibits the activity of articular chondrocytes, leading to disruption of glycolytic energy metabolism and eventual cell death.