Aging is a neurodegenerative disease that leads to cognitive impairment, and an increase in oxidative stress as a major cause is an important factor. It has been reported that aging-related cognitive impairment is associated with increased oxidative damage in several brain regions during aging. As a powerful antioxidant, vitamin C plays an important role in preventing oxidative stress, but due to its unstable chemical properties, it is easily oxidized and thus the activity of antioxidants is reduced. In order to overcome this easily oxidized vulnerability, we developed NXP032 (vitamin C/DNA aptamer complex) that can enhance the antioxidant efficacy of vitamin C using an aptamer. We developed NXP032 (vitamin C/DNA Aptamin C320 complex) that can enhance the antioxidant efficacy of vitamin C using an aptamer. In the present study, we evaluated the neuroprotective effects of NXP032 on aging-induced cognitive decline, oxidative stress, and neuronal damage in 17-month-old female mice. NXP032 was orally administered at 200 mg/kg of ascorbic acid and 4 mg/kg of DNA aptamer daily for eight weeks. Before the sacrifice, a cognitive behavioral test was performed. Administration of NXP032 alleviated cognitive impairment, neuronal damage, microglia activity, and oxidative stress due to aging. We found that although aging decreases the Nrf2-ARE pathway, NXP032 administration activates the Nrf2-ARE pathway to increase the expression of SOD-1 and GSTO1/2. The results suggest that the new aptamer complex NXP032 may be a therapeutic intervention to alleviate aging-induced cognitive impairment and oxidative stress.

Lin28a is an RNA-binding protein involved in the translation and regulation of multiple mRNAs. Lin28a is overexpressed in animal models of brain injury. Similarly, our preliminary study found increased Lin28a expression levels in the animal models four to seven days after chronic cerebral hypoperfusion. Therefore, this current study aimed to evaluate the effects of modulating Lin28a on cognition and brain functions. Vascular dementia (VaD) was induced in 12-week-old male Wistar rats using permanent bilateral common carotid artery occlusion (BCCAO), and these rats were treated with Lin28a siRNA on the fourth and seventh day after BCCAO. From the 42nd day after BCCAO, cognitive behavioral experiments were performed for two weeks. VaD induced by BCCAO resulted in cognitive impairment and microglial activation. Lin28a expression was upregulated after BCCAO. Lin28a siRNA treatment alleviated cognitive impairment and overexpression of GFAP and Iba-1 in the brain. Furthermore, the treatment ameliorated the VaD-induced damage to the blood-brain barrier (BBB) components, including PECAM-1, PDGFRβ, occludin, claudin-9, and ZO-1. CCR6 activation after VaD, associated with BBB disruption, was diminished by treatment with Lin28a siRNA. The treatment inhibited VaD-induced microglial activity and alleviated BBB damage. Thus, blocking Lin28a may alleviate cognitive impairment caused by VaD.

Background: NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2), which is upregulated by a variety of neurodegenerative factors, is neuroprotective and capable of reducing detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. The purpose of this study was to investigate NOX2 expression and the degree of functional recovery following different types of facial nerve injury and assess the effects of antioxidant intervention on nerve regeneration. Methods: A total of 40 mature (6-week-old) male Sprague-Dawley (SD) rats were used. After inducing facial injury (compression injury or cutting injury), we randomized rats into four groups: A, crushing injury only; B, crushing injury with alpha lipoic acid (ALA); C, axotomy only; and D, axotomy with ALA. Recovery from facial nerve injury was evaluated 4 and 14 days after injury by performing behavioral assessments (observational scale of vibrissae movement, modified scale of eye closing and blinking reflex) and measuring changes in NOX2 experimental/control ratio in the injured (left, experimental) facial nerve relative to that in the uninjured (right, control) facial nerve. Results: A comparison between groups according to the type of injury showed a higher NOX2 expression ratio in the axotomy group than in the crushing group (p < 0.001). Regardless of injury type, both groups that received an injection of ALA exhibited a trend toward a higher NOX2 expression ratio, although this difference reached statistical significance only in the axotomy group (p < 0.001). In behavioral assessments, overall behavioral test scores were significantly higher in the crushing injury group immediately after the injury compared with that in the axotomy group. Additionally, in behavioral tests conducted 4 days after the crushing injury, the group injected with ALA showed better results than the group without injection of ALA (p = 0.031). Conclusions: Our study showed that NOX2 expression trended higher with facial nerve injury, exhibiting a significant increase with cutting-type injury. Furthermore, intraperitoneally injection with ALA may be an efficient strategy for accelerating peripheral facial nerve recovery after a crushing injury.

Peripheral facial nerve injury leads to changes in the expression of various neuroactive substances that affect nerve cell damage, survival, growth, and regeneration. In the case of peripheral facial nerve damage, the injury directly affects the peripheral nerves and induces changes in the central nervous system (CNS) through various factors, but the substances involved in these changes in the CNS are not well understood. The objective of this review is to investigate the biomolecules involved in peripheral facial nerve damage so as to gain insight into the mechanisms and limitations of targeting the CNS after such damage and identify potential facial nerve treatment strategies. To this end, we searched PubMed using keywords and exclusion criteria and selected 29 eligible experimental studies. Our analysis summarizes basic experimental studies on changes in the CNS following peripheral facial nerve damage, focusing on biomolecules that increase or decrease in the CNS and/or those involved in the damage, and reviews various approaches for treating facial nerve injury. By establishing the biomolecules in the CNS that change after peripheral nerve damage, we can expect to identify factors that play an important role in functional recovery from facial nerve damage. Accordingly, this review could represent a significant step toward developing treatment strategies for peripheral facial palsy.

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1–13. Among these, TLR2–5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1–5, TLR8, and TLR10–13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.