According to the search strategy, 892 articles were recorded from mentioned databases. The title and summary of the articles were considered by reviewers, then, 173 duplicated articles were removed, and 719 articles were considered for further evaluations. After that, the third reviewer excluded 704 documents based on exclusion criteria and 15 articles were included for the systematic review based on this search strategy (Fig. 3.).

Beata Dabrowska Bouta in 2016 published data through a study has evaluated recognition learning and memory by a novel object recognition test (NORT) on male Wistar adult rats that received nanosilver with 10 ± 4 nm size and dosage of 0.2 mg/kg by gastric tube for 2 weeks. The administration of saline, Ag + , and nano-Ag have shown all groups were similar in NORT analyzed by one-way ANOVA (P > 0.05). So, it was indicated that a low dose of silver could not induce neurotoxicity and changes in the behavioral evaluation [16].

M. Wesierskaa in the year 2018 revealed a finding from the Carousel Maze test with active place avoidance task was done to assess spatial allothetic memory conducted by cognitive coordination processes among male Wistar adult rats which were treated by AgNPs 20 nm ± 5 nm. According to the method, rats were administered orally in two dosages (1 mg/kg + 30 mg/kg) for 28 days, and data are claimed separately as follows: Rats received 30 mg/kg AgNPs: NOAEL value have shown rats from this group performed significantly lower than control group in long-term memory and short-term memory. Rats received 1 mg/kg AgNPs: Data achieved after administration of 1 mg/kg AgNPs has indicated that administered rats by both 1 and 30 mg/kg AgNPs were impaired in their memory function [9].

Katarzyna Dziendzikowska in 2021 claimed according to the article how spatial memory and learning and memory can be impaired by silver nanoparticles 20 ± 5 nm on male Wistar rats by a dosage 0.5 mg/kg. Assessment of spatial memory with shuttle box test: After oral administration for 28 days, an active allothetic place avoidance task was performed and their findings have demonstrated that indexes have to be decreased showing memory assessment, and through this task, all groups performed significantly different which explained a dysfunctional spatial memory in rats that received AgNPs. As a consequence, impairment in memory in all groups was observed [19].

Lucian Hritcu 2011 has published data about deficits in learning and memory after silver nanoparticles administration intraperitoneal by two different sizes (29 nm, 23 nm) on male Wistar rats with 5 µg/kg and 10 µg/kg (both dosages for both sizes) during a week. After that, Y-maze Task and radial arm-maze task were used to evaluate impairments. As a result, through the Y-maze trial, recorded information was reported a remarkable alternation of spatial memory function among rats treated with 5 and 10 doses and both sizes. So, that has been understood by a significant reduction in the continuous change percentage compared with rats in the control group has indicated how short-term memory was impaired. Although groups administered by silver have shown noticeable changes in comparison with control ones, both silver receiver groups were similar in result. Through the radial arm-maze trial, working memory errors (WME) have illustrated a significant different interaction between groups that revealed short-term memory deficient. Meanwhile, both groups treated with AgNPs demonstrated more WME than the control group and they had no significant differences in comparison with each other [21].

Laurie L. Davenport in the year 2015 designed a study on male C57BL/6 mice by Ag intranasal administration. So, particles were used with the size of 25 nm, and a dose of 50 mg/kg was applied by both single doses and repeated doses for 7 days. Finally, spatial learning and memory were assessed by NOR and MWM tests. Findings based on NORT have revealed no significant differences in preference for the novel object in rats who received 50 mg/kg AgNPs for a week compared with the control group. Also, according to data after MWM, there were no remarkable differences among each group on day 1, and travel distances among them were not significantly different which suggested no disability in spatial learning had happened. After the learning phase, a probe trial was performed to evaluate spatial memory that indicated rats treated with 50 mg/kg AgNPs spent less time significantly in the target quadrant. As a result, the probe trial has displayed a reduction in spatial memory through silver toxicity [20].

Mohsen Ghaleb in the year 2021 performed a research project on male mice which were intraperitoneally injected for 35 days with Ag-NPs (40 mg/kg) (19.5 ± 5 nm). After day 35, behavioral evaluation was carried out to assess neurotoxicity induced in mice. As a result, mice exposed to Ag-NPs have shown weak performance through memory tasks in the T-maze experiment. All value parameters including the number of entries into the main arm and food arm, additionally the time taken to spend time in the food arm were significantly different among mice with Ag-NPs administration compared to control mice. Data achieved from shuttle box test have demonstrated that the number of intertribal, stimulated, and reinforced crossings were noticeably decreased in mice treated by Ag-NPs than control group. Also, the males exposed to silver nanoparticles have shown poor learning ability due to spending more time responding to the shock in comparison to the control group. The third evaluation was done by MWM. Collected data from this test have revealed longer escape latencies among longer escape latencies which means impaired learning skills. Also, the probe test time was recorded longer in the treated group compared to the control group, and that displayed an impairment in spatial memory in mice. In conclusion, all these three behavioral tests clarified cognitive behaviors were altered through Ag-NPs [4].

In the year 2022, Shiva Khezri was successful to evaluate silver nanoparticle toxicity on male Wistar rats which were intraperitoneally exposed to Ag-NPs(10 nm) for 21 days with three different dosages of 50, 100, 200, and 400 ppm. The released data from NOR test and Y-maze task have demonstrated that all three administered dosages of Ag-NPs (100, 200, and 400 ppm) were significantly effective in decreasing recognition learning and memory tasks and spatial working memory. Additionally, MWM tests have revealed groups exposed to Ag-NPs with the dosage more than 50 ppm performed with impaired learning skills compared to their control rats during tests based on value parameters including the traveled distance, and escape latency of the training days. Likewise, the time spent in the target quadrant, which give data about spatial memory, shown a noticeable reduction among rats treated with AgNPs (the dosage more than 50 ppm). Although both values were significantly increased among treated rats, the swimming speeds had shown no noticeable differences. So, data obviously displays how Ag-NPs can adversely affect all recognition and spatial learning and memory among male rats treated with dosages more than 50 ppm [17].

In 2012 Ye Liu explained how a low dose (3 mg/kg) and a high dose (30 mg/kg) of silver nanoparticles can cause detrimental impacts on spatial learning and memory. Through this study, male Wistar adult rats received Ag-NPs with the sizes from 32.68 to 38.21 nm and two different dosages for 12 days by nasal administration. Then, the MWM task was applied to evaluate silver neurobehavioral toxicity. Based on the escape latency measurement, all three groups passed this index progressively from day 1 to 4. While both low dose and high dose of silver influenced spatial learning detrimentally in comparison with the control group, control rats could record lower escape latencies. Also, there was a difference among rats who received 3 and 30 mg/kg that is not significant and low doses had been reported with lower records in the same measurement. After the spatial learning phase, a probe test was done to assess the spatial memory that revealed there were two significant differences in both time percentages spent in the target quadrant and the number of crossings on the hidden platform in rats treated by Ag than control ones. In other words, both measurements have decreased among rats who received silver nanoparticles in comparison with the control group, also a high dose of silver was obviously lower. In conclusion, both phases in spatial cognition evaluation could indicate how Ag-np exacerbates spatial skills with various dosages [26].

According to recent research done by Anna A. Antsiferova in 2021, silver nanoparticles with a size of about 34 ± 5 nm can influence C57BL adult male mice's cognitive ability. So, it was evaluated by contextual fear conditioning at a dose of 50 µg per day. There were four experimental groups as follows: rats treated orally by Ag-NP for 30, 60, 120, and 180 days. Consequently, these findings have proven learning ability was not changed by Ag-NPs. Nevertheless, according to data from the long-term contextual memory, there were no remarkable differences in control rats in comparison with Ag-NP groups at 30 days, exceptionally, a significant difference was reported at 180 days of administration which had indicated impaired memory through silver toxicity [24].

Anna Antsiferova during the year 2018 conducted an exploration including four different groups of C57Bl/6 eight-week-old male mice which were orally treated with silver nanoparticles every day with the size 34 ± 2 nm and at concentrations of 2 µg/mL. These mice were divided into four groups which had received Ag-NPs respectively for 30, 60, 120, and 180 days. At the end of each period, the Light–Dark Box test was done to assess learning and memory parameters. According to the similar information received from 30, 60, and 120-days groups, the number of freezing acts was low before performing the electric pulse among both control and treated mice, after the electric pulse, the number of freezing acts significantly increased in both groups which mean Ag exposure for 30 days did not affect the quality of learning in male mice. Also, a slight decrease was observed in both groups in the number of freezing acts in learning during the 24 h time-course. Therefore, contextual memory was not impaired. However, based on data from mice exposed to silver nanoparticles for 180 days, it was concluded that both contextual learning and memory were noticeably impaired [23].

Peidang Liu in the year 2012 by MWM task on adult male ICR mice could evaluate silver detrimental effects in spatial learning and memory, while the particles size was 36.3 ± 1.2 nm, and dosage was determined for three different groups as follows: 10,25, and 50 mg/kg Intraperitoneal administered for 7 days. There was a significant difference between group and day, however, there were no significant differences among mice that experienced Ag exposure, therefore, spatial cognition with no impairment performed perfectly [25].

Jinjin Wu in 2015 started to appraise how silver toxicity during pregnancy can affect male offspring's spatial learning and memory assessed by MWM. So, Ag-NPs were made in the size of 20–50 nm, and have been intraperitoneal administered to mothers in four forms: polyvinyl pyrrolidone (PVP)-coated, uncoated-NPs (0.427mgA pregnant), Ag NPs (0.407 mg/g rat), silver nitrate (0.013 mg/ g rat). Then, male offspring at postnatalday35(PND35) were entered into MWM, and two-way ANOVA analyzed data from the average escape latency to indicate any disability in spatial learning. While data after the third test day has shown a significant increase in the escape latency among rats who received uncoated Ag-NPs compared with other rats treated with a silver. As a result, uncoated Ag-NPs were found as a detrimental factor in the spatial learning of rat offspring. Similarly, in the probe trial rats administered with the uncoated Ag-NPs revealed a significant reduction in spent time in the target quadrant than all other groups, and other groups have shown no reliable difference. In sum, hippocampal neurodevelopment and spatial ability related to cognition can be damaged in rat offspring, if maternal exposure to Ag- NPs during pregnancy has occurred [27].

Similar to Jinjin Wu’s study, Ghaderi in the year 2015 studied NMRI mice exposed prenatally to high doses of silver nanoparticles (0.2 and 2 mg/kg of body weight (BW)) and subcutaneous injection with the size between 5–70 nm. So, female mice were receiving Ag-NPs from gestation day 3, and it was repeated once every three days until parturition. When offspring from both male and female gender were 45 to 49 days old, MWM and passive avoidance learning (PAL) tests were applied to assess their spatial cognition. According to statistical data from the MWM task during 4 days, performances during training trials were improved by a decreasing trend among all rats, although this trend was significantly different. Also, the average moved distance was different in rats that received 2 mg/kg Ag-NPs compared with the control group. The swim average speed during continuous training trials, while there was no statistical variation among rats. Additionally, the Ag-NPs administration was not dependent on sex at during the task. Consequently, mice performances were not affected by gender, and showed a valuable difference for the percentage of traveled distance in the target quadrant). Both distance and the time spent in the target quadrant were recorded lower significantly in rats treated with 2 mg/kg Ag-NPs compared with the control group. A remarkable difference was reported between male and female offspring receiving silver. In conclusion, not only Ag-NPs impaired spatial learning, but also it can detrimentally change spatial memory. Based on the second behavioral task, PAL data analyzed by two-way ANOVA (treatment × sex) has demonstrated that Ag-NPs have not changed indexes evaluated in passive avoidance learning [28].

In 2019 Khaled Greish used Adult male BALB/C mice to evaluate the neurotoxicity of silver nanoparticles. So, they designed this study to administer Ag-NPs in various sizes from 30 to 40 and at a very low dosage (0.1 mg/kg, 2 μg per animal) intravenously. Also, the administration has been conducted by a single injection, 2 injections with a week interval, and 3 injections over 3 weeks. Consequently, rats in the control group were observed normally during the learning assessment and could pass the latency with a reduced trend to find hidden the platform in the pool between the first trial. However, rats that received Ag-NPs were not successful to pass this time with a decreased shift from the initial to the end. Similarly, the distance traveled by rats to reach the submerged platform was recorded to obey a decreased trend, and the AgNPs treated rats could not follow this normal pattern. With a comparison in the escape latency between control rats, and rats receiving one AgNPs administration. But this measurement has not shown any significant variation between the groups treated with one or two AgNPs injections, or between the ones treated with two or three AgNPs administrations. Also, the swimming speed measurement was not observed significantly different among all rats, which indicated that the lower swimming speed has not played an effective role to prevent a reduction trend in the escape latency, and abnormal data from time is associated with learning disability. Owing to the probe trial data, after eliminating the submerged platform, the total time spent was recorded in all 4 quadrants, and time spent by rats in the target quadrant, where the platform was located, could suggest how spatial memory was altered abnormally. In conclusion, analyzed outcomes from this behavioral test directed our finding to impaired spatial learning and memory induced by silver nanoparticles [15].

In 2021, Zinicovscaia managed a project on mice to evaluate the chronic effects of Silver Nanoparticles on cognitive skills. Those mice were exposed to Ag-NPs with a specific concentration (13 mg/ml) and size of 34 ± 1.4 nm by oral Administration through drinking water. One group was treated with silver nanoparticles for 2 months, and the second group for 4 months. At the end of the treatment, a MWM test was applied on mice for 3 groups. Results from the MWM of selective tests have shown that the total moved distance to the platform and the distance to the platform in both groups treated by silver nanoparticles was significantly different compared to the control groups. Then, through evaluating the latency to the platform, it was revealed that both the 2-month experiment and the 4-months experiment revealed significant differences than control mice. Although, other parameters’ values were not significantly noticeable from each day. Results from the MWM of the main test have statistically demonstrated no significant differences in parameters’ values among experimental groups compared to controls. So, it is concluded that Ag-NPs with a dosage of 13 mg/ml and size of 34 ± 1.4 nm in mice treated for 2 and 4 months do not affect spatial learning and memory [22].