Plant extracts and omega-3 improve short-term memory and modulate the microbiota-gut-brain axis in D-Galactose model mice.

BACKGROUND: Aging, characterized by a slow and progressive alteration of cognitive functions, is associated with gut microbiota dysbiosis, low-grade chronic inflammation, as well as increased oxidative stress and neurofunctional alterations. Some nutrients, such as polyphenols, carotenoids, and omega-3, are good candidates to prevent age-related cognitive decline, due to their immunomodulatory, antioxidant and neuroprotective properties. OBJECTIVE: The objective of this study was to demonstrate the preventive effect of a combination of plant extracts (PE) containing Memophenol™ (grapes and blueberries polyphenols) and a patented saffron extract (saffron carotenoids and safranal), and omega-3 (om-3) on cognitive function in a mice model of accelerated aging and to understand the biological mechanisms involved. METHODS: We used an accelerated aging model by injecting 3-month-old male C57Bl6/J mice with D-galactose for 8 weeks, during which they were fed with a balanced control diet, supplemented or not with PE and/or om-3 (n=15-16/group). Short-term memory was evaluated by Y-maze test, following by analyses of hippocampal and intestinal RNA expressions, brain fatty acid and oxylipin amounts and gut microbiota composition (16S rRNA gene sequencing). Statistical analyses were performed (t-test, ANOVA and Pearson's correlation). RESULTS: Our results showed that oral administration of PE, om-3, or both (mix) prevented hippocampus-dependent short-term memory deficits induced by D-galactose (p<0.05). This effect was accompanied by the modulation of gut microbiota, altered by the treatment. PE and the mix increased the expression of antioxidative and neurogenesis markers, such as catalase and DCX, in hippocampus (p<0.05 for both). Moreover, om-3 and the mix showed a higher omega-3 level (p<0.05) and EPA-derived 18-HEPE (p<0.001) in prefrontal cortex. These changes may contribute to the improvement in memory. CONCLUSIONS: These results suggest that the mix of PE and om-3 could be more efficient at attenuating age-related cognitive decline than individual supplementations because it targeted, in mice, the different pathways impaired with aging.

Plant extracts and omega-3 supplementation modulate hippocampal oxylipin profile in response to LPS-induced neuroinflammation.

OBJECTIVE AND DESIGN: Neuroinflammation is a protective mechanism but can become harmful if chronic and/or unregulated, leading to neuronal damage and cognitive alterations. Limiting inflammation and promoting resolution could be achieved with nutrients such as grapes and blueberries polyphenols, saffron carotenoids, and omega-3, which have anti-inflammatory and proresolutive properties. METHODS: This study explored the impact of 18-day supplementation with plant extracts (grape, blueberry and saffron), omega-3 or both (mix) on neuroinflammation induced by lipopolysaccharide (LPS, 250 µg/kg) in 149 mice at different time points post-LPS treatment (30 min, 2 h, 6 h). Inflammatory, oxidative and neuroprotective gene expression; oxylipin quantification; and fatty acid composition were analyzed at each time point. PCA analysis was performed with all these biomarkers. RESULTS: Mix supplementation induced changes in the resolution of inflammation. In fact, the production of proinflammatory mediators in the hippocampus started earlier in the supplemented group than in the LPS group. Pro-resolving mediators were also found in higher quantities in supplemented mice. These changes were associated with increased hippocampal antioxidant status at 6 h post-LPS. CONCLUSIONS: These findings suggest that such dietary interventions with plant extracts, and omega-3 could be beneficial in preventing neuroinflammation and, consequently, age-related cognitive decline. Further research is needed to explore the effects of these supplements on chronic inflammation in the context of aging.

Ramp lesions in ACL deficient knees in children and adolescent population: a high prevalence confirmed in intercondylar and posteromedial exploration.

PURPOSE: Ramp lesions are common in ACL deficient knees. Their diagnosis is difficult and, therefore, they may be underestimated. So far, no study analyzed their prevalence in a pediatric population. The diagnosis of these Ramp lesions is of major clinical relevance because of a frequent misestimating and technic difficulties. Ramp lesions might be associated with residual knee pain and instability after ACL reconstruction. The aim of this study was to evaluate the prevalence of ramp lesions explored through a systematic intercondylar and posteromedial arthroscopic approach during an ACL reconstruction in a pediatric and adolescent population. METHODS: Children and adolescents who underwent an ACL reconstruction were screened prospectively between October 2014 and 2016. The presence or absence of a ramp lesion was evaluated after each of three arthroscopic steps: (1) an anterior approach, (2) an intercondylar inspection, and (3) a posteromedial approach. Ramp lesions were screened at each step and their prevalence was evaluated. Furthermore, their presence was correlated to age, weight, size, sex, and state of the physis (open or closed). Finally, the meniscal status on MRI and arthroscopic findings were compared. RESULTS: Fifty-six patients were analyzed. The median age was 14.0 ± 1.3 years (12-17). The median interval between injury and surgery was 11.5 months (1-108). During step 1 (anterior approach), only 1 ramp lesion (2%) was diagnosed. 13 (23%) ramp lesions were found after inspection through the intercondylar notch. No additional lesions were found with a direct view through the posteromedial approach. No correlation between ramp lesions and side, sex, weight, size, or state of physis was found. 10 ramp lesions out of 13 could not be diagnosed on MRI. CONCLUSIONS: The prevalence of ACL-associated ramp lesions in children and adolescents is similar to adult populations. A systematic inspection through the intercondylar notch is recommended during ACL reconstruction to make a precise diagnosis. The posteromedial approach is essentially useful for meniscal repair LEVEL OF EVIDENCE: Testing, previously developed diagnostic criteria in a consecutive series of patients and a universally applied "gold" standard, Level I.

Posteromedial meniscal tears may be missed during anterior cruciate ligament reconstruction.

PURPOSE: This study aimed to assess the benefit of using an arthroscopic intercondylar view and a posterior medial viewing portal during anterior cruciate ligament (ACL) reconstruction in the diagnosis of posterior horn of the medial meniscus (PHMM) tears. A secondary objective was to determine clinical and radiological risk factors for the PHMM. METHODS: Forty-one patients undergoing isolated ACL reconstruction were prospectively evaluated. At ACL reconstruction, the PHMM was assessed using a standard 30° arthroscope in 3 sequential stages: a "classic" anterolateral portal view, an intercondylar view, and a view through a posteromedial portal. RESULTS: Thirty-nine patients were included (12 female patients and 27 male patients). A posteromedial tear of the medial meniscus was found in 17 patients using the anterolateral portal view. The intercondylar view identified 4 new additional lesions and extensions of 3 previously identified lesions. The posteromedial portal view identified 6 new lesions and 5 extensions of known lesions compared with the anterolateral portal view. Two lesions seen through the posteromedial portal were not identified by either the anterolateral portal view or the intercondylar view. CONCLUSIONS: Tears of the PHMM may be underdiagnosed by intraoperative assessment using only an anterolateral portal view during ACL reconstruction. The intercondylar view combined with a posteromedial portal aids in the diagnosis of PHMM tears and should be considered in routine ACL reconstruction to assess meniscal status, particularly when the interval from injury to surgery is prolonged. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Positioning of the Tibial Tunnel After Single-Bundle ACL Primary Reconstruction on 3D CT scans: A New Method.

PURPOSE: To assess intra-articular tunnel aperture positioning after primary anterior cruciate ligament (ACL) reconstruction with either the reference standard method or the intercondylar area method in a single center using 3-dimensional (3D) computed tomography (CT) scans and to evaluate the intra-articular position of the tibial tunnel relative to the ACL footprint. METHODS: 3D CT scans were performed after 120 single-bundle primary ACL reconstruction cases. The center of the tibial tunnel aperture and the center of the ACL footprint were referenced on axial views of the tibial plateau in the anteroposterior (AP) and mediolateral (ML) planes according to a centimetric grid system including the whole plateau (reference standard). This was compared with a grid system based on intercondylar area bony anatomy. The posterior aspect of intertubercular fossa, anterior aspect of the tibial plateau, medial intercondylar ridge, and crossing point between lateral intercondylar ridge and posterior margin were used as landmarks to define the grid. RESULTS: According to the reference standard method, the center of the tibial tunnel aperture was positioned 0.57 ± 2.62 mm more posterior and 0.67 ± 1.55 mm more medial than the center of the footprint. According to the intercondylar area method, the center of the tibial tunnel aperture was positioned 1.32 ± 2.74 mm more posterior and 0.66 ± 1.56 mm more medial than the center of the footprint. The position difference between the center of the tunnel aperture and the center of the footprint were statistically correlated for both grids, with r = -0.887, P < .001 for AP positioning and r = 0.615, P < .001 for ML positioning. CONCLUSION: This intercondylar area method using arthroscopic landmarks can be used to assess tunnel placement on 3D CT scans after ACL reconstruction. LEVEL OF EVIDENCE: III, retrospective comparative study.