SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797.

Elevated CX3CL1 is associated with severe COVID-19 and neurologic symptoms. We aimed to investigate the potential protective effects of selective CX3CR1 antagonist AZD8797 on SARS-CoV-2-induced neuronal damage, and to identify the underlying mechanisms. K18-hACE2 transgenic mice (n = 37) were randomly divided into control groups and SARS-CoV-2 groups, with and without intraperitoneal administration of vehicle or AZD8797 (2.5 mg/mL/day), following exposure to either a single dose of SARS-CoV-2 inhalation or no exposure. Object recognition and hole board tests were performed to assess memory function. Postinfection 8 days, brain tissues were analyzed for histopathological changes, viral, glial, apoptotic, and other immunohistochemical markers, along with measuring malondialdehyde, glutathione, and myeloperoxidase activities. Serum samples were analyzed for proinflammatory cytokines. The SARS-CoV-2 group showed significant weight loss, neuronal damage, oxidative stress, and impaired object recognition memory, while AZD8797 treatment mitigated some of these effects, especially in weight, apoptosis, glutathione, and MCP-1. Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance.

Possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of mild traumatic brain injury: an investigation.

OBJECTIVE: Apigenin is a plant flavone proven with biological properties such as anti-inflammatory, antioxidant, and antimicrobial effects. This study, it was aimed to examine the possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of the mild traumatic brain injury (TBI) model. METHODS: Wistar albino male rats were randomly assigned to groups: control (n = 9), TBI (n = 9), TBI + vehicle (n = 8), and TBI + apigenin (20 and 40 mg/kg, immediately after trauma; n = 6 and n = 7). TBI was performed by dropping a 300 g weight from a height of 1 m onto the skull under anesthesia. Neurological examination and tail suspension tests were applied before and 24 h after trauma, as well as Y-maze and object recognition tests, after that rats were decapitated. In brain tissue, luminol- and lucigenin-enhanced chemiluminescence levels and cytokine ELISA levels were measured. Histological damage was scored. Data were analyzed with one-way ANOVA. RESULTS: After TBI, luminol (p < .001) and lucigenin (p < .001) levels increased, and luminol and lucigenin levels decreased with apigenin treatments (p < .01-.001). The tail suspension test score increased with trauma (p < .01). According to the pre-traumatic values, the number of entrances to the arms (p < .01) in the Y-maze decreased after trauma (p < .01). In the object recognition test, discrimination (p < .05) and recognition indexes (p < .05) decreased with trauma. There was no significant difference among trauma apigenin groups in behavioral tests. Interleukin (IL)-10 levels, one of the anti-inflammatory cytokines, decreased with trauma (p < .05), and increased with 20 and 40 mg apigenin treatment (p < .001 and p < .01, respectively). The histological damage score in the cortex was decreased in the apigenin 20 mg treatment group significantly (p < .05), but the decrease observed in the apigenin 40 mg group was not significant. CONCLUSION: The results of this study revealed that apigenin 20 and 40 mg treatment may have neuroprotective effects in mild TBI via decreasing the level of luminol and lucigenin and increasing the IL-10 levels. Additionally, apigenin 20 mg treatment ameliorated the trauma-induced cortical tissue damage.

Nesfatin-1 ameliorates oxidative brain damage and memory impairment in rats induced with a single acute epileptic seizure.

AIMS: We aimed to investigate putative neuroprotective effects of nesfatin-1 on oxidative brain injury and memory dysfunction induced by a single epileptic seizure and to compare these effects with those of antiepileptic phenytoin. MAIN METHODS: Wistar albino rats were randomly divided into a control group and pentylenetetrazole (PTZ)-seizure groups pretreated intraperitoneally (ip) with saline or nesfatin-1 (NES-1; 0.3, 1 or 3 µg/kg/day) or phenytoin (PHE; 40 mg/kg/day) or PHE + NES-1 (0.3 µg/kg/day) at 30 min before the single-dose PTZ injection (45 mg/kg; ip). All treatments were repeated at the 24th and 48th h of the provoked epileptic seizure. Passive-avoidance test was performed to assess memory function. The rats were decapitated at the 72nd hour of seizures and brain tissues were analyzed for histopathological changes and for measuring levels of malondialdehyde, glutathione, myeloperoxidase activity and reactive oxygen/nitrogen species. KEY FINDINGS: In parallel to the effects of phenytoin, NES-1 reduced seizure score, elevated antioxidant glutathione content, depressed generation of nitric oxide and protected against seizure-induced neuronal damage. Additionally, increased malondialdehyde levels and elevated glial fibrillary acidic protein immunoreactivity in the cortex and hippocampus were decreased and memory dysfunction was improved by NES-1. However, NES-1 had no impact on myeloperoxidase activity or production of reactive oxygen species in the brain. SIGNIFICANCE: The findings of the present study demonstrate that nesfatin-1 treatment provides neuroprotection against seizure-induced oxidative damage and memory dysfunction by inhibiting reactive nitrogen species and upregulating antioxidant capacity, indicating its potential in alleviating memory deficits and increasing the effectiveness of conventional anti-convulsant therapies.

Effect of Bumetanide on Facial Nerve Regeneration in Rat Model.

OBJECTIVE: We investigated the effects of bumetanide alone and in combination with dexamethasone on facial nerve regeneration in rats with facial paralysis. STUDY DESIGN: A prospective controlled animal study. SETTING: An animal laboratory. SUBJECTS AND METHODS: Facial paralysis was induced in 32 Wistar rats that we then divided into 4 groups: group 1, control; group 2, bumetanide; group 3, dexamethasone; group 4, bumetanide and dexamethasone. Electroneurography was performed 1, 2, and 4 weeks later, and nerve regeneration was evaluated by electron and light microscopy and Western blotting in week 4. RESULTS: Regarding the comparison between preoperative values and week 4, the latency difference in group 1 (1.25 milliseconds) was significantly higher than those of groups 2 to 4 (0.56, 0.34, and 0.10 milliseconds, respectively; P = .001). The latency increment in groups 2 and 3 was higher than that of group 4 (P = .002 and P = .046) in week 4, whereas groups 2 and 3 did not differ significantly (P = .291). Amplitude difference was not statistically significant from week 4 among all groups (all P > .05). The number of myelinated axons was significantly higher in all treatment groups than in the control group (P = .001). Axon number and intensity were significantly higher in group 4 as compared with groups 2 and 3 (P = .009, P = .005). CONCLUSION: After primary neurorrhaphy, dexamethasone and bumetanide alone promoted nerve recovery based on electrophysiologic and histologic measures. Combination therapy was, however, superior.