Parameters of Oxidative Stress and Behavior in Animals Treated with Dexametasone and Submitted to Pentylenetetrazol Kindling

Background and Purpose: Oxidative stress (OS) is defined as an excessive production of reactive oxygen species that cannot be neutralized by the action of antioxidants, but also as an alteration of the cellular redox balance. The relationship between OS and epilepsy is not yet fully understood. The objective of this study was to evaluate the effect of dexamethasone on OS levels and memory in the kindling model induced by pentylenetetrazole.Methods: The animals were divided in six groups: control group that received no treatment, vehicle group treated with vehicle, diazepam group, and groups treated with dexamethasone (1, 2 and 4 mg/kg). Treated animals received pentylenetetrazole in alternated days for 15 days. Inhibitory avoidance test was conducted in 2 hours and OS was evaluated after animal sacrifice.Results: Regarding the treatment with dexamethasone, there was no significant difference when compared to the control groups in relation to the inhibitory avoidance test. On OS levels, there was a decrease in catalase activity levels in the hippocampus and an increase in thiobarbituric acid reactive substances and glutathione peroxidase levels in the hippocampus.Conclusions: The anticonvulsant effect of dexametasone remains uncertain. Immunological mechanisms, with the release of cytokines and inflammatory mediators, seem to be the key to this process. The mechanisms that generate OS are probably related to the anticonvulsant effects found.

The Behavior Avoidance Test: Association With Symptom Severity and Treatment Outcome in Obsessive-Compulsive Disorder

Behavior therapy of obsessive-compulsive disorder (OCD) aims to reduce avoidance, rituals, and discomfort in OCD-relevant situations. The Behavioral Avoidance Test (BAT) measures these behavior-related outcomes in individually challenging OCD-related situations. The association of the BAT with OCD severity measures and its relevance for treatment outcome is, however, still unclear. The current study investigates with a retrospective analysis of a subsample of a pilot study, (1) if reactions on the BAT are related to OCD severity measures in an OCD sample (n = 28), (2) if treatment with two variants of cognitive-behavior therapy (exposure and response prevention vs. metacognitive therapy) changes the BAT scores and (3) if these changes as well as pretreatment BAT avoidance are relevant for OCD treatment outcome as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Participants rated avoidance, ritual, and discomfort in three individually challenging OCD-related situations before and after therapy. For one of these situations, BAT dimensions were rated by the therapist and an independent rater in addition to the patients' ratings. Correlational analyses found significant correlations between BAT discomfort and OCD severity measures like the Y-BOCS. A repeated measures ANOVA with pre- and posttest scores showed that all three BAT dimensions significantly decreased during both treatments. Hierarchical regression analyses (controlling for Y-BOCS pretest scores) revealed that changes in BAT discomfort as well as pretreatment BAT avoidance scores predicted the Y-BOCS posttest score. These findings suggest that the BAT is a distinct measure of behavior-related outcomes partly being relevant for OCD treatment outcome.

Butea superba Roxb. Extract Ameliorates Scopolamine-Induced Cognitive and Memory Impairment in Aged Male Rats

Butea superba Roxb. (B. superba) is a herb that has been used for rejuvenation, to improve sexual performance, or to prevent erectile dysfunction function. Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is the main cause of progressive dementia. This study aimed to investigate the amelioration for cognitive and memory dysfunction of B. superba ethanolic extract (BSE), a possible mechanism of action, and its toxicity. The results from the Y-maze test, novel object recognition test, and passive avoidance test exhibited that the administration of BSE at 50 mg/kg (BSL) and 200 mg/kg (BSH) could ameliorate scopolamine-induced cognitive impairment in all behavior testing. Moreover, BSE could prevent the cognitive deficit in a dose-dependent manner in a passive avoidance test. Furthermore, BSE inhibited acetylcholinesterase’s (AChE) ex vivo activity in the cerebral cortex and hippocampus. Also, the in vitro and ex vivo antioxidative effects of BSE revealed that BSE had free radical scavenging activities in both DPPH and FRAP assay. Furthermore, male rats treated with BSE at 200 mg/kg/day for two weeks could significantly increase serum testosterone compared with control ( P < 0.05 ). The GC-MS analysis and previous studies revealed that BSE contained propanoic acid, 3,3′-thiobis-, didodecyl ester, oleic acid, gamma-sitosterol, and stigmasterol which may play an important role in cognitive and memory impairment prevention. The toxicity test of BSE in rats at 50 and 200 mg/kg/day for two weeks showed that relative organ weight, serum creatinine, ALT, ALP, and CBC levels of both treated groups were not significantly different compared to the CON ( P > 0.05 ). These results suggest that BSE may not be toxic to the vital organ and blood. In conclusion, BSE has the potential to be developed as a health supplement product or medicine for AD prevention and treatment.

Neuroprotective Effects of Ceftriaxone Involve the Reduction of Aβ Burden and Neuroinflammatory Response in a Mouse Model of Alzheimer’s Disease

Ceftriaxone (CEF) is a safe and multipotent antimicrobial agent that possesses neuroprotective properties. Earlier, we revealed the restoration of cognitive function in OXYS rats with signs of Alzheimer’s disease (AD)-like pathology by CEF along with its modulating the expression of genes related to the system of amyloid beta (Aβ) metabolism in the brain. The aim of this study was to determine the effects of CEF on behavior, Aβ deposition, and associated neuroinflammation using another model of an early AD-like pathology induced by Aβ. Mice were injected bilaterally i.c.v. with Aβ fragment 25–35 to produce the AD model, while the CEF treatment (100 mg/kg/day, i.p., 36 days) started the next day after the surgery. The open field test, T-maze, Barnes test, IntelliCage, and passive avoidance test were used for behavioral phenotyping. Neuronal density, amyloid accumulation, and the expression of neuroinflammatory markers were measured in the frontal cortex and hippocampus. CEF exhibited beneficial effects on some cognitive features impaired by Aβ neurotoxicity including complete restoration of the fear-induced memory and learning in the passive avoidance test and improved place learning in the IntelliCage. CEF significantly attenuated amyloid deposition and neuroinflammatory response. Thus, CEF could be positioned as a potent multipurpose drug as it simultaneously targets proteostasis network and neuroinflammation, as well as glutamate excitotoxicity, oxidative pathways, and neurotrophic function as reported earlier. Together with previous reports on the positive effects of CEF in AD models, the results confirm the potential of CEF as a promising treatment against cognitive decline from the early stages of AD progression.

Thiamine Alleviates Cognitive Impairment and Epileptogenesis by Relieving Brain Inflammation in PTZ-induced Kindling Rat Model

Epileptogenesis, the process by which the brain becomes epileptic, is related to neuroinflammation, hyperexcitability, and as a result cognitive deficits. Evidence suggests that therapeutic strategies targeting pathologic brain inflammation have emerged as a promising approach that prevents or disease-modifying therapy for epileptogenesis. Therefore, the PTZ kindling model of epilepsy was utilized to assess the neuroprotective role of thiamine in epileptogenesis. Male rats were exposed to PTZ-induced kindling and pretreated with low thiamine (25 mg/kg) or high thiamine (50 mg/kg). Cyclooxygenase (COX-1 and COX-2), interleukin 1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor-κB (NF-κB) concentrations in the brain were analyzed using biochemical assays. Cognitive function was evaluated using the passive avoidance test. Thiamine ameliorated epileptogenesis and enhanced the rats' performance in the passive avoidance test. Also, thiamine significantly decreased the level of neuroinflammatory mediators in the brain induced by PTZ. These results provide evidence that thiamine alleviates PTZ-induced neuroinflammation and cognitive impairments.

Lactobacillus plantarum GKM3 Promotes Longevity, Memory Retention, and Reduces Brain Oxidation Stress in SAMP8 Mice

(1) Background: An age-related cognitive decline is commonly affecting the life of elderly with symptoms involved in progressive impairments to memory and learning. It has been proposed that probiotics could modulate age-related neurological disorders via the gut–brain axis. (2) Methods: To investigate the anti-aging effect of probiotic Lactobacillus plantarum GKM3, both survival tests and cognitive experiments were conducted in the SAMP8 mice model. The six-month-old SAMP8 (n = 20 in each gender) were fed with probiotic GKM3 at a dosage of 5.1 × 109 and 1.0 × 109 cfu/ kg B.W./day until their natural death. Then, the life span was investigated. Three-month-old SAMP8 (n = 10 in each gender) were administered GKM3 for 14 weeks. Then, the behavior tests and oxidation parameters were recorded. (3) Results: GKM3 groups showed significantly increased latency in the passive avoidance test and time of successful avoidance in the active avoidance test. The TBARS and 8-OHdG from mice brains also showed a significant reduction in the groups treated with GKM3. In addition, lower accumulation of the amyloid-β protein was found in SAMP8 mice brains with the supplement of GKM3. (4) Conclusions: These results indicated that L. plantarum GKM3 delayed the process of aging, alleviated age-related cognitive impairment, and reduced oxidative stress.

A Study on the Evaluation Method of Autonomous Vehicle for Fixed Targets

Recently, the automobile industry aims to commercialize autonomous vehicles, standardization and research and development are actively underway based on the specifications of automotive electronic control systems and the verification of functional errors. Based on this, autonomous driving technology is becoming more advanced, and it is preparing for an era of full autonomous driving through V2X technology convergence. It is also, expanding the models of ADAS applied vehicles such as FCW, BSD, LCA. Based on this, research is also actively underway to secure safety of vehicles and pedestrians, such as V2X, Localization, Fail Safe, to supplement the limitations of sensor-based autonomous driving. In this regard, this study proposes a theoretical formula for longitudinal relative distance computation for autonomous vehicles evaluation method, and uses test device such as DGPS to collects and verify data. In addition, a scenario was proposed for the fixed target, based on this, four types of test were formed to conduct the actual test, and the relative distances were compared, analyzed and verified. Comparative analysis results, in the second test of the first test scenario, the avoidance test of the fixed target in driving own lane, the minimum error rate was 0.5%, and in the second test of fourth test scenario, the avoidance test of the fixed target in driving own lane, the maximum error rate was 7.4%. The main cause of error is, it was judged as an error due to sensor recognition, depending on the scenario progress method, the condition of the test path, and the weather such as sunlight. In the future, we plan to conduct an evaluation on moving target.

Effect of Streblus asper Leaf Extract on Scopolamine-Induced Memory Deficits in Zebrafish: The Model of Alzheimer’s Disease

Streblus asper (SA) is well known as a folk medicinal plant in Asian countries. The effect of SA extract on preventing memory impairment in zebrafish induced by scopolamine was investigated. Male zebrafish, Danio rerio, were divided into 6 groups including the control, scopolamine 200 μM (SCO), scopolamine plus rivastigmine 1.5 mg/kg (RV + SCO), and scopolamine plus SA extract at doses of 200, 400, and 800 mg/kg (SA200 + SCO, S400 + SCO, and SA800 + SCO), respectively. Spatial memory was evaluated by the colour-biased appetite conditioning T-maze test, while fear memory was measured by the inhibitory avoidance test. In the spatial memory test, results showed that the RV + SCO group had the best time spent ratio in the T-maze, followed by SA800 + SCO, SA400 + SCO, SA200 + SCO, control, and SCO group, respectively, but with no statistical significance. For the fear memory test, zebrafish that received SA at doses of 200, 400, and 800 mg/kg had significantly increased latency time as 21.75 ± 4.59, 23.75 ± 13.01, and 18.20 ± 18.84 min, respectively, when compared to the SCO group (9.80 ± 10.45 min). These results suggested that SA extract attenuated memory impairment in an inhibitory avoidance test related to fear memory. Our findings can be useful for further research to develop SA extract as a health product to ameliorate the symptoms of Alzheimer’s disease.

Effects of memantine on the passive avoidance test in young rats

Alzheimer’s disease (AD) is a long-lasting progressive neurodegenerative disease that degrades memory and cognitive function and is often complicated by disorientation and other psychiatric syndromes. At present, to improve the condition of patients with AD, for their treatment, use the drug memantine. The drug is a noncompetitive antagonist of NMDA glutamate receptors in the brain. The present experiments aimed to test the influence of memantine on the memory processes in rats. We used the passive avoidance test “Stepdown”. The latter is used to assess memory function based on the association formed between a particular environment that an animal is learning to avoid and a negative stimulus in the form of a weak electric shock to the feet. We found that memantine significantly, twice, decreased the latency time step-down from the platform in rats during their familiarization with the chamber. The rats became more determined and less afraid of the unknown environment under memantine. Memantine significantly affected the emotionality of young rats, which leads to errors in the passive avoidance test. However, it did not impair memory. It can be concluded that memantine induces a shift toward greater excitability in rats.