CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its biological properties through interaction with one dedicated CX3CR1 receptor which belongs to a family of G protein-coupled receptors (GPCR). The CX3CL1/CX3CR1 axis acts in many physiological phenomena including those occurring in the central nervous system (CNS), by regulating the interactions between neurons, microglia, and immune cells. Apart from the role under physiological conditions, the CX3CL1/CX3CR1 axis was implied to have a role in different neuropathologies such as traumatic brain injury (TBI) and spinal cord injury (SCI). CNS injuries represent a serious public health problem, despite improvements in therapeutic management. To date, no effective treatment has been determined, so they constitute a leading cause of death and severe disability. The course of TBI and SCI has two consecutive poorly demarcated phases: the initial, primary injury and secondary injury. Recent evidence has implicated the role of the CX3CL1/CX3CR1 axis in neuroinflammatory processes occurring after CNS injuries. The importance of the CX3CL1/CX3CR1 axis in the pathophysiology of TBI and SCI in the context of systemic and direct local immune response is still under investigation. This paper, based on a review of the literature, updates and summarizes the current knowledge about CX3CL1/CX3CR1 axis involvement in TBI and SCI pathogenesis, indicating possible molecular and cellular mechanisms with a potential target for therapeutic intervention.
Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.
To determine whether a combination of constraint-induced movement therapy and physiotherapy in stroke patients using different constraint regimens (sling versus voluntary constraint) changes or reduces motor deficits, the amount of functional use of the arm and whether the effects of treatment continue after 12 months. Forty-seven stroke patients were stratified and randomly divided into intensive physiotherapy programmes focused on regaining arm functions. Neurorehabilitation Unit of IInd Department of Neurology at Institute of Psychiatry and Neurology in Warsaw. Patients were randomly allocated to: the sling-constraint group (n = 24) or to the voluntary-constraint group (n = 23). Massed practice with the paretic arm (5 hours/day for 15 consecutive working days). Sling-constraint group had their arm immobilized in a hemi-sling during therapy. In addition, individual, 1-hour physiotherapy sessions were conducted in both groups. Rivermead Motor Assessment (RMA) Arm scale, (0–15), Motor Activity Log – Quality of Movement (MAL-QOM) (0–5 for 30 daily tasks). There was no significant difference between groups after therapy (MAL-QOM mean change for sling group 0.78, SD = 0.46 and for voluntary-constraint group 0.84, SD = 0.48; P = 0.687). All treated patients retained mean gains in real-world arm use (MAL-QOM) mean scores after 12 months follow-up compared with posttreatment values but there was no significant difference between groups (comparison of estimated mean change of MAL-QOM stated 0.23. 95% confidence interval = −0.04–0.50). Voluntary activity constraint in the intact arm is equivalent to sling, standard constraint during massed practice of paretic arm.
29 December 2022 in Journal of Pediatric Rehabilitation Medicine
PURPOSE: Restrictions related to the COVID-19 pandemic can negatively affect patients who require physiotherapy. This study aimed to analyze the consequences of limited physiotherapy on the functional state of children with neuromuscular diseases (NMD). In addition, the caregivers’ well-being and caregiver opinions on physiotherapy were analyzed. METHODS: A questionnaire was shared with parents of children with NMD immediately after the COVID-19 lockdown. The survey included questions regarding the physical and mental condition of children and parents before the pandemic and during lockdown as well as their views on physiotherapy and telephysiotherapy. Statistical analysis was performed using the Wilcoxon Matched-Pairs Signed Ranks test, Spearman’s Rank Correlation test, McNemar test, and Chi-square test. RESULTS: Parents of 235 children participated in the study. Results indicated that children devoted more time to physiotherapy before the pandemic than during the lockdown period, which was true for those living in cities and the countryside. The functional state of 50.2% of the children deteriorated during the lockdown, in the opinion of their parents. Significant correlations were found between limited physiotherapy time and the deterioration of children’s functional condition, ability to maintain a standing position, and increased anxiety. The majority of parents reported increased levels of fear and anxiety (72.8%), fatigue (67.7%), and pain (53.2%). In-person physiotherapy was rated significantly higher than telephysiotherapy by parents. CONCLUSIONS: Limited access to physiotherapy and shorter therapy times may lead to functional deterioration in children with NMD, but this assumption needs to be objectively confirmed. According to the parents’ opinions, telephysiotherapy is less beneficial than direct physiotherapy but may support therapy conducted directly by a physiotherapist. Results based on subjective parental opinions may be helpful in planning future projects.
MMP-9 and S100B, the proteins involved in blood-brain barrier integrity, are widely studied as biomarkers in many diseases, including epilepsy. They are elevated in epilepsy patients both interictally and following motor seizures. To determine whether motor activity influences their serum concentrations, we investigated the effects of brief, seizure-like physical exercise on serum MMP-9 and S100B levels in healthy individuals. Participants performed two different 5-min exercise protocols mimicking the motor activity of bilateral tonic–clonic seizures, one of the sets of exercises that contribute to to muscle failure. Serum samples were collected before exercise, 3 h after exercise, and the next day (time points 0, 3 h, and 24 h). Our results demonstrated that both sets of motor exercises led to a similar increase in MMP-9 levels, while neither affected S100B levels. No significant differences in MMP-9 levels were observed due to muscle failure. We suggest that the increase in MMP-9 seen after seizures is induced partially by peripheral mechanisms, such as muscle contraction. S100B appears to be a promising biomarker in epilepsy, as it is not induced by physical activity but does increase following seizures. Further research is needed to fully elucidate the mechanisms underlying biomarker release in epilepsy and to determine the specific contributions of muscle contractions versus other seizure-related processes.