Systematic Review Of Animal Studies Research Articles

Photobiomodulation in promoting increased Skin Flap Viability: a systematic review of animal studies.

Necrosis is common in skin flap surgeries. Photobiomodulation, a noninvasive and effective technique, holds the potential to enhance microcirculation and neovascularization. As such, it has emerged as a viable approach for mitigating the occurrence of skin flap necrosis. The aim of this systematic review was to examine the scientific literature considering the use of photobiomodulation to increase skin-flap viability. The preferred reporting items for systematic reviews and meta-analyses (PRISMA), was used to conducted systematic literature search in the databases PubMed, SCOPUS, Elsevier and, Scielo on June 2023. Included studies investigated skin-flap necrosis employing PBMT irradiation as a treatment and, at least one quantitative measure of skin-flap necrosis in any animal model. Twenty-five studies were selected from 54 original articles that addressed PBMT with low-level laser (LLL) or light-emitting diode (LED) in agreement with the qualifying requirements. Laser parameters varied markedly across studies. In the selected studies, the low-level laser in the visible red spectrum was the most frequently utilized PBMT, although the LED PBMT showed a similar improvement in skin-flap necrosis. Ninety percent of the studies assessing the outcomes of the effects of PBMT reported smaller areas of necrosis in skin flap. Studies have consistently demonstrated the ability of PBMT to improve skin flap viability in animal models. Evidence suggests that PBMT, through enhancing angiogenesis, vascular density, mast cells, and VEGF, is an effective therapy for decrease necrotic tissue in skin flap surgery.

The biological effects of Piezocision™ on bone for accelerated tooth movement: A systematic review of animal studies

Objectives: This systematic review aimed to assess the biological response at tissue, cellular, and molecular levels following Piezocision™ surgery, and its efficacy in accelerating orthodontic tooth movement.Material and methods: A systematic review of the literature was conducted across 4 databases following the PRISMA guidelines up to May 2022. Prospective controlled animal studies involving healthy animals under active orthodontic treatment assisted by corticotomy performed with a piezotome (Piezocision™) published in the English language without time restrictions were included. The article selection, data extraction and risk of bias assessment (SYRCLE tool) were performed by two independent blinded review authors.Results: Out of 738 articles screened, 10 studies were included with various level of bias. Biological responses were categorized into tissue, cellular, and molecular levels. Tissue-level changes included a global decrease in bone mineral content post-Piezocision™. At the cellular level, increased bone turnover activity was noted. Molecularly, elevated RANKL and OPG expression, along with increased TRAP+ and cytokines, were observed after Piezocision™. Studies confirmed Piezocision's efficacy, reporting 1.35 to 3.26 times faster tooth movements, peaking between the 3rd and 50th day post-surgery. Biological responses were transient, reversible, and proportional to surgical insult, with reactivation possible through a second Piezocision™.Conclusions: After Piezocision™ surgery, a transient and reversible biological response was described at the tissue, cellular and molecular levels, which induced faster orthodontic tooth movements. This biological response could be re-activated by an additional Piezocision™ and is proportional to the surgical injury. Systematic review registration: Prospero CRD42022303237.

Plant-Derived Substances for Prevention of Necrotising Enterocolitis: A Systematic Review of Animal Studies.

Inflammation, oxidative injury, and gut dysbiosis play an important role in the pathogenesis of necrotising enterocolitis (NEC). Plant-derived substances have historically been used as therapeutic agents due to their anti-inflammatory, antioxidant, and antimicrobial properties. We aimed to review pre-clinical evidence for plant-derived substances in the prevention and treatment of NEC. A systematic review was conducted using the following databases: PubMed, EMBASE, EMCARE, MEDLINE and Cochrane Library (PROSPERO CRD42022365477). Randomized controlled trials (RCTs) and quasi-RCTs that evaluated a plant-derived substance as an intervention for NEC in an animal model of the illness and compared pre-stated outcomes (e.g., clinical severity, severity of intestinal injury, mortality, laboratory markers of inflammation and oxidative injury) were included. Sixteen studies (n = 610) were included in the systematic review. Ten of the sixteen included RCTs (Preterm rat pups: 15, Mice: 1) reported mortality and all reported NEC-related histology. Meta-analysis showed decreased mortality [12/134 vs. 27/135; RR: 0.48 (95% CI: 0.26 to 0.87); p = 0.02, 10 RCTs] and decreased NEC in the experimental group [24/126 vs. 55/79; RR: 0.34 (95% CI: 0.22 to 0.52); p < 0.001, 6 RCTs]. Markers of inflammation (n = 11) and oxidative stress (n = 13) improved in all the studies that have reported this outcome. There was no significant publication bias for the outcome of mortality. Plant-derived substances have the potential to reduce the incidence and severity of histologically diagnosed NEC and mortality in rodent models. These findings are helpful in guiding further pre-clinical studies towards developing a food supplement for the prevention of NEC in preterm infants.

Effect of Lithium on Orthodontic Tooth Movement: a Systematic Review of Animal Studies.

This study aimed to systematically review the effect of lithium on orthodontic tooth movement (OTM). The focus question was "does lithium have an effect on OTM?" A systematic search was conducted using indexed databases and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The quality assessment of the selected studies was performed according to the systematic review center for laboratory animal experimentation. Five of the initially identified 656 articles fulfilled the eligibility criteria and were selected for this review. The studies reported that lithium administration lowered the rate of OTM by inducing a reduction in the number of osteoclasts and possibly inhibiting osteoclastogenesis. These studies further showed an increase in bone density and bone volume by promoting the Wnt/ß-catenin signaling pathway and osteoblastogenesis. It was also noted that lithium reduced orthodontically induced root resorption during experimental OTM. Further, standardized studies are warranted to understand the impact of lithium in OTM. Overall, the risk of bias for 3 studies was very high, high in 1 study, and moderate in 1 study. On an experimental level in animals, lithium decreased the rate of OTM during the active treatment phase by increasing bone density and bone volume and reducing root resorption. In addition, lithium may enhance alveolar bone formation during orthodontic retention. Clinically, this may impact the orthodontic treatment duration in patients receiving lithium, and further studies are needed to understand the true impact of lithium on OTM.

Biological response to endodontic treatment in one versus two-visit: a systematic review and meta-analysis of animal studies.

To perform a systematic review of animal studies that compared the histopathological characteristics between teeth with apical periodontitis after endodontic treatment in one or two visits. This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) - CRD42022340849. Studies were collected from PubMed/MEDLINE, LILACS, EMBASE, Livivo, SciELO, Web of Science, Scopus, and Cochrane Library and manual and gray literature searches. Animal studies that evaluated histological characteristics after endodontic treatment of teeth with apical periodontitis in one or two visits were included. Risk of bias analysis of the included studies was performed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Data synthesis of the included studies with quantitative data was performed, and meta-analysis was conducted with the Comprehensive Meta-Analysis software, using the random effects model and odds ratio (OR). Eighteen studies met the inclusion criteria (Kappa = 0.891). Meta-analyses indicated values in inflammatory infiltrate intensity with effect size of 5.5% (95% CI: 0.020-0.148; p < 0.001), periodontal ligament thickness: 25.6% (95% CI: 0.134-0.487; p < 0.001), dentin resorption: 13% (95% CI: 0.015-1.141; p = 0.066), cementum resorption: 7.1% (95% CI: 0.015-0.325; p = 0.001), bone resorption: 1.4% (95% CI: 0.002-0.130; p < 0.001), mineralized tissue resorption: 42.8% (95% CI: 0.110-1.671; p = 0.222), biological apical sealing: 13.1% (95% CI: 0.055-0.314; p < 0.001), and presence of microorganisms: 10.3% (95% CI: 0.014-0.747; p = 0.025). When considering animal studies, the two-visit endodontic treatment, using calcium hydroxide-based intracanal medication, resulted in better biological repair characteristics. A two-visit endodontic treatment with calcium hydroxide-based intracanal medication yields superior histopathological outcomes.

Potential of Solanum betaceum to improve cognition: A systematic review of animal studies

Context: Solanum betaceum is rich in bioactive compounds associated with various health applications, including plausible benefits on cognitive impairment caused by neurodegenerative diseases such as Alzheimer’s disease (AD). Aims: To investigate the potential benefit of consuming S. betaceum to alleviate cognitive and memory decline. Methods: The review was conducted as a systematic review of an in vivo animal study. A search was performed of five databases using the keywords: “solanum betaceum”, “S. betaceum”, “tamarillo”, “neurodegenerative diseases”, “memory loss”, “cognitive impairment”. SYRCLE tool was used to assess the risk of bias. Data on the underlying molecular mechanisms of behavioral efficacy was additionally collected. Results: A total of 66 journals were retrieved from the databases, resulting in 3 eligible studies. All included studies used albino rats as an AD animal model that were accustomed to laboratory conditions for about a week prior to the disease induction. In two studies, aluminum chloride (AlCl3) was utilized to induce memory deficit, while another study used cigarette smoke. The result indicated that S. betaceum contained compounds such as phenolic and anthocyanin, which were plausibly responsible for the positive cognitive outcomes through molecular interaction with intracellular signaling protein cascades associated with anti-inflammation, brain oxygenation, synaptic plasticity, and cell viability. Further preclinical studies are needed to confirm these potentials. Conclusions: This systematic review of the current evidence on the behavioral and biological influences of S. betaceum administration on AD animal models pointed out that the fruit might improve cognitive performance and prevent cognitive deterioration raised by several neurotoxins.

Potential benefits of microalgae intake against metabolic diseases: beyond spirulina-a systematic review of animal studies.

Microalgae are a diverse source of bioactive molecules, such as polyphenols, carotenoids, and omega-3 fatty acids, with beneficial properties in biomarkers of metabolic diseases. Unlike the rest of the microalgae genera, Arthrospira sp., commonly called spirulina, has been widely studied. This review aims to describe the current knowledge about microalgae, besides spirulina, focusing on their beneficial properties against metabolic diseases. A systematic research of MEDLINE (via PubMed), Cochrane, and Scopus databases was conducted to identify relevant studies published after January 2012. In vivo animal studies including microalgae consumption, except for spirulina, that significantly improved altered biomarkers related to metabolic diseases were included. These biomarkers included body weight/composition, glucose metabolism, lipid metabolism, oxidative damage, inflammation markers, and gut microbiota. After the literature search and the implementation of inclusion and exclusion criteria, 37 studies were included in the revision out of the 132 results originally obtained after the application of the equation on the different databases. Data containing 15 microalgae genera were included reporting on a wide range of beneficial results at different levels, including a decrease in body weight and changes in plasma levels of glucose and lipoproteins due to molecular alterations such as those related to gene expression regulation. The most reported beneficial effects were related to gut microbiota and inflammation followed by lipid and glucose metabolism and body weight/composition. Microalgae intake improved different altered biomarkers due to metabolic diseases and seem to have potential in the design of enriched foodstuffs or novel nutraceuticals. Nevertheless, to advance to clinical trials, more thorough/detailed studies should be performed on some of the microalgae genera included in this review to collect more information on their molecular mechanisms of action.

Osseointegration in additive-manufactured titanium implants: A systematic review of animal studies on the need for surface treatment

The objective of the systematic review is to find an answer to a question: “Do surface treatments on titanium implants produced by additive manufacturing improve osseointegration, compared to untreated surfaces?“. This review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2020) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022321351). Searches were performed in PubMed, Scopus, Science Direct, Embase, and Google Scholar databases on March 22nd, 2022. Articles were chosen in 2 steps by 2 blinded reviewers based on previously selected inclusion criteria: articles in animals that addressed the influence of surface treatments on osseointegration in implants produced by additive manufacturing. Articles were excluded that (1) did not use titanium surface, 2) that did not evaluate surface treatments, 3) that did not described osseointegration, 4) Studies with only in vitro analyses, clinical studies, systematic reviews, book chapters, short communications, conference abstracts, case reports and personal opinions.). 1003 articles were found and, after applying the eligibility criteria, 17 were used for the construction of this review. All included studies found positive osseointegration results from performing surface treatments on titanium. The risk of bias was analyzed using the SYRCLE assessment tool. Surface treatments are proposed to promote changes in the microstructure and composition of the implant surface to favor the adhesion of bone cells responsible for osseointegration. It is observed that despite the benefits generated by the additive manufacturing process in the microstructure of the implant surface, surface treatments are still indispensable, as they can promote more suitable characteristics for bone-implant integration. It can be concluded that the surface treatments evaluated in this systematic review, performed on implants produced by additive manufacturing, optimize osseointegration, as it allows the creation of a micro-nano-textured structure that makes the surface more hydrophilic and allows better contact bone-implant.

Mechanism of action of quercetin in rheumatoid arthritis models: meta-analysis and systematic review of animal studies.

Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, doseselection and the improvement of quercetin's bioavailability remain to be explored.

Effects of Epothilone Administration on Locomotion Recovery after Spinal Cord Injury: A Systematic Review of Animal Studies.

This is a systematic review and meta-analysis of existing evidence regarding the possible effects of epothilones on spinal cord injury (SCI). This study aimed to investigate the possible effects of epothilone administration on locomotion recovery in animal models of SCI. Despite increasing rates of SCI and its burden on populations, no consensus has been reached about the possible treatment modality for SCI. Meanwhile, low-dose epothilones have been reported to have positive effects on SCI outcomes. Electronic databases of Web of Science, Scopus, Embase, and Medline were searched using keywords related to epothilones and SCI until the end of 2020. Two researchers screened the articles, and extracted data were analyzed using STATA ver. 14.0. Final results are reported as a standardized mean difference (SMD) with a 95% confidence interval (CI). After the screening, five studies were included in the analysis. Rats were used in all the studies. Two types of epothilones were used via intraperitoneal injection and were shown to have positive effects on the motor outcomes of samples with SCI (SMD, 0.87; 95% CI, 0.51 to 1.23; p =0.71). Although a slightly better effect was observed when using epothilone B, the difference was not significant (coefficient, -0.50; 95% CI, -1.52 to 0.52; p =0.246). The results of this study suggest that epothilones have positive effects on the improvement of motor function in rats, when administered intraperitoneally until a maximum of 1 day after SCI. However, current evidence regarding the matter is still scarce.

Role of prebiotic dietary fiber in periodontal disease: A systematic review of animal studies.

Periodontitis is a chronic inflammatory condition affecting the supporting structures of a tooth in the oral cavity. The relationship between dietary fiber and periodontitis is poorly understood. The objective of this systematic review is to investigate if an intake of dietary fiber modulates periodontal disease in animal models and any concomitant effects on systemic inflammation, microbiota and their metabolites. Animal studies using periodontitis models with any form of fiber intervention were included. Studies with comorbidities that were mutually inclusive with periodontitis and animals with physiological conditions were excluded. Search strategy with MeSH and free-text search terms were finalized and performed on the 22nd of September 2021.CINAHL Complete, EMBASE, MEDLINE, SciVerse Scopus® and Web of Science Core Collection databases were used to identify studies. SYRCLE's risk of bias tool and CAMARADES were used for quality assessment. Results were synthesized utilizing Covidence© web-based platform software to remove duplicates, and the remaining studies were manually filtered. A total of 7,141 articles were retrieved from all databases. Out of 24 full-text articles assessed for eligibility, four studies (n = 4) were included. Four studies involved the use of β-(1,3/1,6)-glucan (n = 3) and mannan oligosaccharide (n = 1) at differing dosages for different study durations. All studies utilized a ligature-induced model of periodontitis in rats, either Wistar (n = 3) or Sprague-Dawley (n = 1). A dose-dependent relationship between the increased fiber intake and decrease in alveolar bone loss and pro-inflammatory markers was observed. The number of included studies is limited and narrow in scope. They highlight the importance of pre-clinical trials in this field with broader dietary fiber intervention groups before proceeding to clinical trials. The use of dietary fiber as an intervention shows promise in the reduction of inflammatory conditions like periodontitis. However, further research is required to delineate the relationship between diet and its effects on microbiota and their metabolites such as short chain fatty acids in animal models of periodontitis.

Progesterone and contraceptive progestin actions on the brain: A systematic review of animal studies and comparison to human neuroimaging studies

In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.

Does photobiomodulation on the root surface decrease the occurrence of root resorption in reimplanted teeth? A systematic review of animal studies.

PROSPERO Identifier: CRD42022349891.

Renoprotective effects of the ginger (Zingiber officinale) on Diabetic kidney disease, current knowledge and future direction: a systematic review of animal studies

ObjectiveDiabetic kidney disease affects approximately 40% of diabetic patients and is the leading cause of chronic kidney disease (CKD) worldwide. As a result, preventing renal complications in diabetic patients is critical. Ginger (Zingiber Officinale Rosco) is a popular spice and natral medicine. The present study was a systematic review focused on the existing evidence of the renoprotective effect of ginger extract on some features of diabetic kidney disease.MethodsThe literature was searched in online databases such as PubMed, Scopus, EMBASE, ProQuest databases, and Google Scholar from inception to July 2022.ResultsThis review included 41 articles that met the eligibility criteria. Ginger supplementation was found to be associated with a significant decrease in blood glucose in 28 studies. Nine studies showed a significant reduction in malondialdehyde (MDA) after supplementation. Also, seventeen studies showed decreased serum levels of creatinine. Fifteen studies reported a decrease in total cholesterol (TC) and fourteen studies showed a lowered triglycerides (TG) concentrations. In twenty-six studies, ginger reduced renal injuries due to diabetes.ConclusionGinger may improve blood sugar indices, lipid profile, some inflammatory markers, oxidative stress, and pathologic injuries in diabetic kidney disease. However, future well-designed clinical trials and meta-analyses are required for a solid consensus.

Potential Use of Hyperbaric Oxygen Therapy in Orthodontic Treatment: A Systematic Review of Animal Studies.

Understanding the fundamental principles of tooth movement could reduce the duration of treatment and achieve a stable outcome, resulting in patient satisfaction. Hyperbaric oxygen therapy was a modality in which a patient inhaled 100% O2 while subjected to high atmospheric pressure. Hyperbaric oxygen therapy facilitated the supply of oxygen to the human body's organs and tissues and served a variety of applications, including patient care and wound treatment. This review article aimed to describe animal studies of the potential effects of hyperbaric oxygen therapy in orthodontic therapy. It was conducted using a systematic literature review method, including searching PubMed and Google Scholar for publications relevant to the research topics. The search was filtered to include only research on orthodontic treatment and hyperbaric oxygen therapy and was published in any year. Articles that did not specify biological components of orthodontic tooth movement (OTM) were excluded. The Preferred Reporting Items identified the papers for the Systematic Reviews and Meta-Analyses (PRISMA) strategy, which resulted in the selection of 11 publications. Hyperbaric oxygen therapy affected parameters of biomarkers representing the clinical, molecular, and cellular biology of bone formation and resorption in periodontal tissues in responding to orthodontic physical forces, including alkaline phosphatase, collagen synthesis, osteoblast, osteoclast, osteocyte, type I collagen, vascular endothelial growth factor, osteocalcin, fibroblast, matrix metalloproteinase-8, transforming growth factor-β, partial pressure of oxygen, partial pressure of carbon dioxide, trabecular bone density, and tooth mobility. Hyperbaric oxygen therapy induced an inflammatory response to follow OTM events during active orthodontic therapy. Hyperbaric oxygen therapy might play a role in the tissue healing process during passive treatment. Nonetheless, additional research should be conducted to establish the efficacy of hyperbaric oxygen therapy in orthodontics.

May alcoholic and non-alcoholic drinks affect the rate of orthodontic tooth movement? A systematic review of animal studies.

Humans may consume various beverages in everyday life. Previous research has shown that the administration of different substances (medicinal or not) may affect bone turnover and, thus, orthodontic tooth movement. It would be anticipated that the substances contained in beverages could have an impact on tooth movement, as well. To investigate in a systematic way and appraise the quality of the available evidence from animal studies regarding the impact of various drinks or the main ingredients included in beverages on the rate of orthodontic tooth movement. Search without restriction in six databases (including grey literature) and hand searching were performed until March 2022. We looked for controlled animal studies investigating the effect of drinks, or the main ingredients included in beverages, on the rate of orthodontic tooth movement. After study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. The quality of available evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation. The initially identified records were finally reduced to nine studies conducted on animals. Carbonated soft drinks were shown to decrease the rate of tooth movement, but alcohol consumption did not have an impact. Exploratory meta-analysis showed that caffeine exhibited an acceleratory effect after 3 weeks of force application. Exploratory meta-regression results indicated that high dosages of caffeine reduced the rate of tooth movement. The located animal experiments reported that caffeine accelerates, carbonated drinks decelerate, while alcohol does not affect the rate of orthodontic tooth movement. However, due to various limitations it remains unclear whether caffeine, alcohol, or carbonated drinks finally influence tooth movement in animal studies. Open Science Framework (https://osf.io/jyhbd/).

The effects of caffeine following hypoxic-ischemic encephalopathy: A systematic review of animal studies

BackgroundCaffeine is believed to be neuroprotective in preterm and term infants, despite the conflicting data on its effects on the developing brain in animal models. We aimed to conduct a systematic review with meta-analysis assessing the effects of caffeine on the prevention and treatment of neurological morbidity caused by hypoxic-ischemic encephalopathy (HIE) in preclinical studies. MethodsRandomized and non-randomized control studies in animal models of HIE reporting caffeine administration within the first ten days of life were included. Primary outcomes were behavioral tests that served as surrogates for cognition, memory, motor coordination, and gait; secondary outcomes pertained to structural neurologic changes. Screening for inclusion, risk of bias and data extraction were performed independently by two authors. ResultsSeven studies met inclusion: 5 studies were conducted in rats and 2 in mice. All studies were performed in full-term animals, and the majority of studies used animals of both sexes (5/7). In six studies, caffeine was administered intraperitoneally to the pups, while in the remaining study, it was delivered via the drinking water of the lactating dams. The doses of caffeine ranged from 5 to 20 mg/kg; in one study, caffeine dosage was 0.3 mg/L in the drinking water of lactating dam. The mortality rate was reported only in three studies. Caffeine had a positive effect on overall functional outcome (SDM 0.92(95%CI 0.25 to 1.59)). Animals treated with caffeine performed better on Morris water maze and rotarod tests (SDM −1.39(95%CI −0.36 to −2.41)) and (SDM 1.03(95%CI 0.03 to 2.04)), respectively. Caffeine treated animals performed worse on open field test compared to the controls (SDM −1.11(95%CI −3.01 to 0.80)). The overall quality of the included studies was limited. ConclusionsEarly caffeine exposure in preclinical rodent models of HIE is associated with improved selective functional and neurological outcomes, although the certainty of the evidence is limited. To validate the therapeutic efficacy of caffeine as a neuroprotective adjuvant, there is a need to explore its effects in larger animal models, which will help guide the design of relevant clinical trials.

Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies.

Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson's disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.

The anti-Leishmania potential of bioactive compounds derived from naphthoquinones and their possible applications. A systematic review of animal studies.

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments.

Effects of Caffeine Consumption on Attention Deficit Hyperactivity Disorder (ADHD) Treatment: A Systematic Review of Animal Studies.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. ADHD impairments arise from irregularities primarily in dopamine (DA) and norepinephrine (NE) circuits within the prefrontal cortex. Due to ADHD medication’s controversial side effects and high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caffeine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evidence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal studies is lacking. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to 1 September 2021. Caffeine treatment increases attention and improves learning, memory, and olfactory discrimination without altering blood pressure and body weight. These results are supported at the neuronal/molecular level. Nonetheless, the role of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that the cognitive effects of caffeine found in animal models could be translated to human ADHD, particularly during adolescence.