Effects of intra-articular injection of platelet-rich plasma on the inflammatory process and histopathological characteristics of cartilage and synovium in animals with osteoarthritis: a systematic review with meta-analysis.

BACKGROUND: Osteoarthritis (OA) affects the entire joint, causing structural changes in articular cartilage, subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles that afflicts millions of people globally, leading to persistent pain and diminished quality of life. The intra-articular use of platelet-rich plasma (PRP) is gaining recognition as a secure therapeutic approach due to its potential regenerative capabilities. However, there is controversial clinical data regarding efficacy of PRP for OA treatment. In this context, gathering scientific evidence on the effects of PRP in treating OA in animal models could provide valuable insights into understanding its impact on aspects like cartilage health, synovial tissue integrity, and the inflammatory process in affected joints. Thus, the objective of this study was to assess the effects of PRP injections on inflammation and histopathological aspects of cartilage and synovium in animal models of OA through a comprehensive systematic review with meta-analysis. METHODS: A electronic search was conducted on Medline, Embase, Web of Science, The Cochrane Library, LILACS, and SciELO databases for relevant articles published until June 2022. A random-effects meta-analysis was employed to synthesize evidence on the histological characteristics of cartilage and synovium, as well as the inflammatory process. The GRADE approach was utilized to categorize the quality of evidence, and methodological quality was assessed using SYRCLE's RoB tool. RESULTS: Twenty-one studies were included in the review, with twelve of them incorporated into the meta-analysis. PRP treatment demonstrated superior outcomes compared to the control group in terms of cartilage histology (very low quality; p = 0.0002), synovium histology (very low quality; p < 0.0001), and reductions in proinflammatory markers, including IL-1 (low quality; p = 0.002), IL-6 (very low quality; p < 0.00001), and TNF-α (very low; p < 0.00001). However, PRP treatment did not yield a significant impact on PDGF-A levels (very low quality; p = 0.81). CONCLUSION: PRP appears capable of reducing proinflammatory markers (IL-1, IL-6, TNF-α) and mitigating cartilage and synovium damage in animals with OA. However, the levels of evidence of these findings are low to very low. Therefore, more rigorous studies with larger samples are needed to improve the quality of evidence. PROSPERO REGISTRATION: CRD42022250314.

Neuronal activation of cerebellum functional circuits in motor and non-motor functions in mice.

The cerebellum is involved in the control of balance, movement and the acquisition of motor skills. Scientific and technological advances have shown that the cerebellum also participates in non-motor functions, such as emotional control, memory and language. However, which cerebellar areas and functional circuits are predominantly activated in these different functions is not known. The current study analyzed the neuronal activation of cerebellar areas and other brain structures (e.g., hippocampus, amygdala, prelimbic cortex and infralimbic cortex) after exposure to rotarod and inhibitory avoidance behavioral models to establish possible neuronal circuits for motor and non-motor functions. Naïve male Swiss albino mice weighing 25 to 35 g were used. The animals were subjected to three conditions for behavioral evaluation: inhibitory avoidance, which is a model used to infer emotional memory; rotarod, which assesses motor performance and motor learning; and housing box/control. The mice remained in their housing box in Condition 1. Mice in Condition 2 were exposed to the inhibitory avoidance box for 2 days, and mice in Condition 3 were exposed to the rotarod for 3 days. The animals were euthanized after the last exposure to the apparatus then perfused with paraformaldehyde. Brains were extracted and sectioned for immunofluorescence analysis of c-Fos protein in pre-established structures. Images of the brain structures were obtained, and neuronal activation was analyzed microscopically. One-way analysis of variance was used, followed by Tukey's post-hoc test. There was no significant difference in c-Fos expression in lobe VI of the cerebellum between the different conditions. Differences in c-Fos expression were observed in the basolateral amygdala, infralimbic cortex and prelimbic cortex, which are relevant to emotional processes, after exposure to the evaluation apparatuses. Pearson's r correlation coefficient test showed a positive correlation between the variables of structures related to emotional processes. We concluded that there was no significant difference in c-Fos expression in lobe VI of the cerebellum after exposure of the animals to the evaluation apparatus. However, there was a difference in c-Fos expression in other brain structures related to emotional processes after exposure of animals to the apparatus.

Asymmetry in children with unilateral cerebral palsy during sit-to-stand movement: Cross-sectional, repeated-measures and comparative study.

BACKGROUND: We aimed to compare motor strategies adopted by children with unilateral Cerebral Palsy and typically developing children during the performance of sit-to-stand. METHODS: Eleven children with unilateral cerebral palsy and 20 typically developing children were evaluated. Kinematic and kinetic analysis of the sit-to-stand movement was performed. Three seat heights were evaluated: neutral (90° of hip-knee-ankle flexion), elevated to 120% of the neutral height, and lowered to 80% of the neutral height. As outcome variables, we considered sit-to-stand duration (temporal); initial, final and maximal sagittal angles and range of motion of trunk, pelvis, hip, knee, and ankle (kinematics); the peak of vertical ground reaction force (kinetics), and asymmetric index. Effect size is represented by η2p. FINDINGS: We found that for the lowered seat, all groups presented increased flexion of lower limbs and trunk to initiate sit-to-stand (p≤0.012; η2p = 0.41-0.84), increased peak flexion of trunk, hip and knee (p≤0.01; η2p = 0.39-0.88), increased range of motion of knee and trunk (p≤0.01; η2p = 0.45-0.85) and the duration of sit-to-stand (p≤0.05 η2p = 0.23-0.56). Children with unilateral cerebral palsy presented increased posterior pelvic tilt (p≤0.01) and decreased hip flexion of both lower limbs (p≤0.01) for all seat heights and moved their non-affected limb backward in the lowered seat (p≤0.01). Asymmetry was observed for the final and the maximal angles of the ankle in neutral and lowered seats in unilateral cerebral palsy (asymmetry index = 3.3-5.8%). INTERPRETATION: The lowered seat height led to adaptive motor strategies in children with unilateral cerebral palsy, which should be considered in clinical practice.