Locomotor Impairment Research Articles

Motor deficits are associated with increased glial cell activation in the hypothalamus and cerebellum of young rats subjected to cerebral palsy

Cerebral palsy (CP) is a syndrome characterized by a wide range of sensory and motor damage, associated with behavioral and cognitive deficits. The aim of the present study was to investigate the potential of a model of CP using a combination of perinatal anoxia and sensorimotor restriction of hind paws to replicate motor, behavioral and neural deficits. A total of 30 of male Wistar rats were divided into Control (C, n = 15), and CP (CP, n = 15) groups. The potential of the CP model was assessed by evaluating food intake, the behavioral satiety sequence, performance on the CatWalk and parallel bars, muscle strength, and locomotor activity. The weight of the encephalon, soleus, and extensor digitorum longus (EDL) muscles, and the activation of glial cells (microglia and astrocytes) were also measured. The CP animals showed delayed satiety, impaired locomotion on the CatWalk and open field test, reduced muscle strength, and reduced motor coordination. CP also reduced the weight of the soleus and muscles, brain weight, liver weight, and quantity of fat in various parts of the body. There was also found to be an increase in astrocyte and microglia activation in the cerebellum and hypothalamus (arcuate nucleus, ARC) of animals subjected to CP.

Effectiveness of Polyphenols on Perinatal Brain Damage: A Systematic Review of Preclinical Studies.

Polyphenol supplementation during early life has been associated with a reduction of oxidative stress and neuroinflammation in diseases caused by oxygen deprivation, including cerebral palsy, hydrocephaly, blindness, and deafness. Evidence has shown that perinatal polyphenols supplementation may alleviate brain injury in embryonic, fetal, neonatal, and offspring subjects, highlighting its role in modulating adaptative responses involving phenotypical plasticity. Therefore, it is reasonable to infer that the administration of polyphenols during the early life period may be considered a potential intervention to modulate the inflammatory and oxidative stress that cause impairments in locomotion, cognitive, and behavioral functions throughout life. The beneficial effects of polyphenols are linked with several mechanisms, including epigenetic alterations, involving the AMP-activated protein kinase (AMPK), nuclear factor kappa B (NF-κB), and phosphoinositide 3-kinase (PI3K) pathways. To highlight these new perspectives, the objective of this systematic review was to summarize the understanding emerging from preclinical studies about polyphenol supplementation, its capacity to minimize brain injury caused by hypoxia-ischemia in terms of morphological, inflammatory, and oxidative parameters and its repercussions for motor and behavioral functions.

Melatonin reduces β-amyloid accumulation and improves short-term memory in streptozotocin-induced sporadic Alzheimer's disease model.

Melatonin is a hormone secreted by the pineal gland, it can be associated with circadian rhythms, aging and neuroprotection. Melatonin levels are decreased in sporadic Alzheimer's disease (sAD) patients, which suggests a relationship between the melatonergic system and sAD. Melatonin may reduce inflammation, oxidative stress, TAU protein hyperphosphorylation, and the formation of β-amyloid (Aβ) aggregates. Therefore, the objective of this work was to investigate the impact of treatment with 10mg/kg of melatonin (i.p) in the animal model of sAD induced by the intracerebroventricular (ICV) infusion of 3mg/kg of streptozotocin (STZ). ICV-STZ causes changes in the brain of rats similar to those found in patients with sAD. These changes include; progressive memory decline, the formation of neurofibrillary tangles, senile plaques, disturbances in glucose metabolism, insulin resistance and even reactive astrogliosis characterized by the upregulation of glucose levels and glial fibrillary acidic protein (GFAP). The results show that ICV-STZ caused short-term spatial memory impairment in rats after 30 days of STZ infusion without locomotor impairment which was evaluated on day 27 post-injury. Furthermore, we observed that a prolonged 30-day treatment with melatonin can improve the cognitive impairment of animals in the Y-maze test, but not in the object location test. Finally, we demonstrated that animals receiving ICV-STZ have high levels of Aβ and GFAP in the hippocampus and that treatment with melatonin reduces Aβ levels but does not reduce GFAP levels, concluding that melatonin may be useful to control the progression of amyloid pathology in the brain.

Rehabilitation of Neurological Disorders Using Body Weight Supported Treadmill Training - A Brief Review

Treadmill walking with the help of body weight support or without body weight support through a harness connected to an overhead support system, is a method of rehabilitating locomotor impairments in patients suffering from various disorders which affect normal gait/locomotion and is becoming increasingly popular. Body weight supported treadmill training (BWSTT) is a recent therapeutic training / technique that is being used for rehabilitation of patients with neurological walking disorders such as stroke, spinal cord injuries and cerebral palsy and parkinson’s disease. Further research to be carried out for establishing a definitive treatment protocol for BWSTT in these disease states Keywords: Body weight supported treadmill training, stroke, spinal cord injuries, cerebral palsy.

Sorbitol reduction via AT-007 (govorestat) ameliorates synaptic dysfunction and neurodegeneration in models of sorbitol dehydrogenase deficiency.

Sorbitol dehydrogenase (SORD) deficiency has been identified as the most frequent autosomal recessive form of hereditary neuropathy. Loss of SORD causes high sorbitol levels in tissues due to the inability to convert sorbitol to fructose in the two-step polyol pathway, leading to degenerative neuropathy. The underlying mechanisms of sorbitol-induced degeneration have not been fully elucidated, and no current FDA-approved therapeutic options are available to reduce sorbitol levels in the nervous system. Here, in a Drosophila model of SORD deficiency, we showed synaptic degeneration in the brain, neurotransmission defect, locomotor impairment, and structural abnormalities in the neuromuscular junctions. In addition, we found reduced ATP production in the brain and reactive oxygen species accumulation in the central nervous system (CNS) and muscle, indicating mitochondrial dysfunction. Applied Therapeutics, Inc has developed a CNS-penetrant next-generation aldose reductase inhibitor (ARI), AT-007 (govorestat), which inhibits the conversion of glucose to sorbitol. AT-007 significantly reduced sorbitol levels in patient-derived fibroblasts, iPSC-derived motor neurons, and Drosophila brains. AT-007 feeding in Sord-deficient Drosophila mitigated synaptic degeneration and significantly improved synaptic transduction, locomotor activity, and mitochondrial function. Moreover, AT-007 treatment significantly reduced ROS accumulation in Drosophila CNS, muscle, and patient-derived fibroblasts. These findings uncover the molecular and cellular pathophysiology of SORD neuropathy and provide a potential treatment strategy for patients with SORD deficiency.

Electrocortical Dynamics of Usual Walking and the Planning to Step over Obstacles in Parkinson's Disease.

The neural correlates of locomotion impairments observed in people with Parkinson's disease (PD) are not fully understood. We investigated whether people with PD present distinct brain electrocortical activity during usual walking and the approach phase of obstacle avoidance when compared to healthy individuals. Fifteen people with PD and fourteen older adults walked overground in two conditions: usual walking and obstacle crossing. Scalp electroencephalography (EEG) was recorded using a mobile 64-channel EEG system. Independent components were clustered using a k-means clustering algorithm. Outcome measures included absolute power in several frequency bands and alpha/beta ratio. During the usual walk, people with PD presented a greater alpha/beta ratio in the left sensorimotor cortex than healthy individuals. While approaching obstacles, both groups reduced alpha and beta power in the premotor and right sensorimotor cortices (balance demand) and increased gamma power in the primary visual cortex (visual demand). Only people with PD reduced alpha power and alpha/beta ratio in the left sensorimotor cortex when approaching obstacles. These findings suggest that PD affects the cortical control of usual walking, leading to a greater proportion of low-frequency (alpha) neuronal firing in the sensorimotor cortex. Moreover, the planning for obstacle avoidance changes the electrocortical dynamics associated with increased balance and visual demands. People with PD rely on increased sensorimotor integration to modulate locomotion.

Antidepressant-like activity of a brain penetrant HCN channel inhibitor in mice.

Changes in Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) channel function have been linked to depressive-like traits, making them potential drug targets. However, there is currently no peer-reviewed data supporting the use of a small molecule modulator of HCN channels in depression treatment. Org 34167, a benzisoxazole derivative, has been patented for the treatment of depression and progressed to Phase I trials. In the current study, we analysed the biophysical effects of Org 34167 on HCN channels in stably transfected human embryonic kidney 293 (HEK293) cells and mouse layer V neurons using patch-clamp electrophysiology, and we utilised three high-throughput screens for depressive-like behaviour to assess the activity of Org 34167 in mice. The impact of Org 34167 on locomotion and coordination were measured by performing rotarod and ledged beam tests. Org 34167 is a broad-spectrum inhibitor of HCN channels, slowing activation and causing a hyperpolarising shift in voltage-dependence of activation. It also reduced I h-mediated sag in mouse neurons. Org 34167 (0.5mg/kg) reduced marble burying and increased the time spent mobile in the Porsolt swim and tail suspension tests in both male and female BALB/c mice, suggesting reduced depressive-like behaviour. Although no adverse effects were seen at 0.5mg/kg, an increase in dose to 1mg/kg resulted in visible tremors and impaired locomotion and coordination. These data support the premise that HCN channels are valid targets for anti-depressive drugs albeit with a narrow therapeutic index. Drugs with higher HCN subtype selectivity are needed to establish if a wider therapeutic window can be obtained.

Сhanges of trace elements in the cerebellum and their influence on the rats behavior in elevated plus maze in the acute period of mild blast-induced brain injury

BackgroundIn connection with the widespread use of explosive devices in military conflicts, in particular in Ukraine, is relevant to detect the biometals changes in the cerebellum and determine the presence of their influence on the behavior changes of rats in the elevated plus maze in the acute period of a mild blast-traumatic brain injury (bTBI). MethodsThe selected rats were randomly divided into 3 groups: Group I - Experimental with bTBI (with an excess pressure of 26–36 kPa), Group II - Sham and Group III - Intact. Behavior studies was in the elevated plus maze. Brain spectral analysis was with using of energy dispersive X-ray fluorescence analysis, after obtaining the quantitative mass fractions of biometals, the ratios of Cu/Fe, Cu/Zn, Zn/Fe were calculated and the data between the three groups were compared. ResultsThe results showed an increase in mobility in the experimental rats, which indicates functional disorders of the cerebellum in the form of maladaptation in space. Changes in cognitive activity also is an evidence of cerebellum suppression, which is indicated by changes in vertical locomotor activity. Grooming time was shortened. We established a significant increase in Cu/Fe and Zn/Fe ratios in the cerebellum, a decrease in Cu/Zn. ConclusionsChanges in the Cu/Fe, Cu/Zn, and Zn/Fe ratios in the cerebellum correlate with impaired locomotor and cognitive activity in rats in the acute posttraumatic period. Accumulation of Fe on the 1st and 3rd day leads to disturbance of the Cu and Zn balance on the 7th day and starts a "vicious cycle" of neuronal damage. Cu/Fe, Cu/Zn, and Zn/Fe imbalances are secondary factors in the pathogenesis of brain damage as a result of primary bTBI.

Determinants of access of frail, community-residing older adults to geriatricians in Ontario.

Little is known about determinants of access to community-based geriatricians. The Geriatric 5Ms™ describe geriatricians' core competencies and inform referrals to specialists for older adults with complex needs. We explored the association of the Geriatric 5Ms™ and other characteristics with outpatient access to geriatricians by home care (HC) clients. This was a population-based, retrospective cohort study of frail community-dwelling HC clients (≥60 years) with complex needs (n = 196,444). Health assessment information was linked to health services data in Ontario, Canada, 2012-2015. Multivariable generalized estimating equations were used to identify characteristics associated with geriatrician contact (≥1 visit in 90 days post-HC admission), including derived Geriatric 5Ms™ score, and predisposing, enabling, and need factors obtained from clinical assessments. Only 5.2% of the cohort had outpatient geriatrician contact in Ontario, Canada. Derived Geriatric 5Ms™ score was associated with higher odds of contact, but the model had modest discriminatory power (c-statistic = 0.67). In the broader multivariable model, based on empirically included factors and adjusted for regional differences, age, worsening of decision-making, dementia, hallucinations, Parkinsonism, osteoporosis, and caregiver distress/institutionalization risk were associated with higher odds of geriatrician contact. Female sex, difficulties accessing home, impaired locomotion, recovery potential, hemiplegia/hemiparesis, and cancer, were associated with lower odds of contact. This model had good discriminatory power (c-statistic = 0.77). Few frail, community-dwelling older adults receiving HC had any outpatient geriatrician contact. While the derived Geriatric 5Ms™ score was associated with contact, a broader empirical model performed better than the Geriatric 5Ms™ in predicting contact with an outpatient geriatrician. Contact was mainly driven by conditions common in older adults, but evidence suggests that geriatricians are not evaluating the most medically complex and unstable older adults in the community. These findings suggest a need to re-examine the referral process for geriatricians and the allocation of limited specialized resources.

Creatine supplementation increases postnatal growth and strength and prevents overexpression of pro-inflammatory interleukin 6 in the hippocampus in an experimental model of cerebral palsy

ABSTRACT Objectives: The aim of this study was thus to evaluate the effect of Cr supplementation on morphological changes and expression of pro-inflammatory cytokines in the hippocampus and on developmental parameters. Methods: Male Wistar rat pups were submitted to an experimental model of CP. Cr was administered via gavage from the 21st to the 28th postnatal day, and in water after the 28th, until the end of the experiment. Body weight (BW), food consumption (FC), muscle strength, and locomotion were evaluated. Expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were assessed in the hippocampus by quantitative real-time polymerase chain reaction. Iba1 immunoreactivity was assessed by immunocytochemistry in the hippocampal hilus. Results: Experimental CP caused increased density and activation of microglial cells, and overexpression of IL-6. The rats with CP also presented abnormal BW development and impairment of strength and locomotion. Cr supplementation was able to reverse the overexpression of IL-6 in the hippocampus and mitigate the impairments observed in BW, strength, and locomotion. Discussion: Future studies should evaluate other neurobiological characteristics, including changes in neural precursor cells and other cytokines, both pro- and anti-inflammatory.

Carrying eggs uphill: are costs of reproduction stronger on steeper slopes?

Locomotor impairment during pregnancy is a well-documented cost of reproduction, but most empirical studies have not incorporated ecological complexity, such as locomotion on sloping inclines rather than horizontal surfaces. Biomechanical factors suggest that carrying a heavy burden-including shifts in the body's centre of mass-may impair locomotor ability even more when an animal is running uphill. If so, then measuring costs of reproduction on horizontal racetracks may underestimate these costs in nature for arboreal species. To evaluate this prediction, we measured the pregnancy-induced reduction in speed for jacky dragons (Amphibolurus muricatus) at inclines ranging from 0 to 45°. Both pregnancy and steeper slopes reduced lizard performance, but pregnancy did not exacerbate the locomotor decrement on steeper racetracks. An ability to maintain mobility on steep slopes during pregnancy may be a target of selection in arboreal taxa. To understand the evolutionary context of locomotion-based costs of reproduction, we also need studies on the relationship between organismal performance and ecologically relevant measures such as predation risk.

The alleviative effect of Calendula officinalis L. extract against Parkinson's disease-like pathology in zebrafish via the involvement of autophagy activation.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, effective preventative or therapeutic agents for PD remain largely limited. Marigold Calendula officinalis L. (CoL) has been reported to possess a wide range of biological activities, but its neuroprotective activity including anti-neurodegenerative diseases is unclear. Here, we aim to investigate whether the extract of CoL (ECoL) has therapeutic activity on PD. We identified the chemical composition of flavonoid, an important active ingredient in ECoL, by a targeted HPLC-Q-TOF-MS analysis. Subsequently, we evaluated the anti-PD effect of ECoL by using zebrafish PD model induced by 1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine (MPTP). After ECoL+MPTP co-treatments, the changes of dopaminergic neurons, neural vasculature, nervous system, and locomotor activity were examined, respectively. The expressions of genes related to neurodevelopment and autophagy were detected by RT-qPCR. Further, the interaction between autophagy regulators and ECoL flavonoids was predicted using molecular docking method. As a result, 5 kinds of flavonoid were identified in ECoL, consisting of 121 flavones and flavonols, 32 flavanones, 22 isoflavonoids, 11 chalcones and dihydrochalcones, and 17 anthocyanins. ECoL significantly ameliorated the loss of dopaminergic neurons and neural vasculature, restored the injury of nervous system, and remarkably reversed the abnormal expressions of neurodevelopment-related genes. Besides, ECoL notably inhibited the locomotor impairment in MPTP-induced PD-like zebrafish. The underlying anti-PD effect of ECoL may be implicated in activating autophagy, as ECoL significantly upregulated the expressions of genes related to autophagy, which contributes to the degradation of α-synuclein aggregation and dysfunctional mitochondria. Molecular docking simulation showed the stable interaction between autophagy regulators (Pink, Ulk2, Atg7, and Lc3b) and 10 main compounds of flavonoid in ECoL, further affirming the involvement of autophagy activation by ECoL in anti-PD action. Our results suggested that ECoL has the anti-PD effect, and ECoL might be a promising therapeutic candidate for PD treatment.

The Neonicotinoid Imidacloprid Impairs Learning, Locomotor Activity Levels, and Sucrose Solution Consumption in Bumblebees (Bombus terrestris).

Bumblebees carry out the complex task of foraging to provide for their colonies. They also conduct pollination, an ecosystem service of high importance to both wild plants and entomophilous crops. Insecticides can alter different aspects of bumblebee foraging behavior, including the motivation to leave the hive, finding the right flowers, handling flowers, and the ability to return to the colony. In the present study, we assessed how the neonicotinoid imidacloprid affects bumblebees' foraging behavior after exposure to four different treatment levels, including field-realistic concentrations (0 [control], 1, 10, and 100 μg/L), through sucrose solution over 9 days. We observed the behavior of several free-flying bumblebees simultaneously foraging on artificial flowers in a flight arena to register the bees' complex behavior postexposure. To conduct a detailed assessment of how insecticides affect bumblebee locomotor behavior, we used video cameras and analyzed the recordings using computer vision. We found that imidacloprid impaired learning and locomotor activity level when the bumblebees foraged on artificial flowers. We also found that imidacloprid exposure reduced sucrose solution intake and storage. By using automated analyses of video recordings of bumblebee behavior, we identified sublethal effects of imidacloprid exposure at field-realistic doses. Specifically, we observed negative impacts on consumption of sucrose solution as well as on learning and locomotor activity level. Our results highlight the need for more multimodal approaches when assessing the sublethal effects of insecticides and plant protection products in general. Environ Toxicol Chem 2023;42:1337-1345. © 2023 SETAC.

IMPROVING THE METHODOLOGY OF PHYSICAL THERAPY IN ATHLETES WITH INJURIES OF THE KNEE JOINT CONNECTIVE APPARATUS

Description and results of the action developed programs of kinesiotherapy with a combination of kinesiotape to restore impaired locomotor functions of the knee joint and the possibility of continuation playing sports after arthroscopic operations for damage to the ligamentous apparatus.
 Injuries of the musculoskeletal system (MS) are quite common, especially in athletes. According to statistics, up to 50-70% of all ORA injuries occur in the knee joint. Most often, this type of injury is received by athletes, representatives of complex coordination sports and martial arts. Among injuries to the knee joint, injuries to the ligaments, which later cause post-traumatic instability, take second place after damage to the menisci.
 35 patients with injuries of the ligamentous apparatus of the CS (12 women and 23 men) who underwent arthroscopic surgery took part in our study. The patients were active athletes in various sports, in particular game sports. Patients were divided into two groups (the main group and the comparison group) depending on the kind of restorative treatment program. The main group included 23 people whose average age was (24.3±3.0) years. Patients of this group received a rehabilitation program in the conditions of an educational and scientific center Department of Physical Therapy, Occupational Therapy of PNU named after Vasyl Stefanyk. The comparison group (CP) consisted of 12 people, the average age of which was (23.8±3.1) years, who underwent rehabilitation in the polyclinic department of the 1st city polyclinic.
 The individual program of physical therapy for OG patients included kinesiotherapy and massage muscles of the lower limb, physiotherapeutic procedures and the use of kinesiotape. Kinesiotherapy included therapeutic gymnastics of independent classes, massage for the prevention of contracture of the CS and atrophy of the thigh muscles. Various types of massage were used - classic manual massage with passive movements in the joints, self-massage and hydro massage. Physiotherapy procedures were aimed at reducing swelling and pain, preventing the development of the inflammatory process. Patients were prescribed electrophoresis of painkillers, UV irradiation, and UHF or laser therapy, applications of ozokerite or paraffin. These procedures contribute to the stimulation of lymph and blood circulation, trophic processes in the joints, increasing the amplitude of movements and restoring the strength of the muscles of the limb.
 In order to objectify the results of the restorative treatment, the functional ability of the lower limb was assessed using the Lovett muscle test (six-point assessment of muscle strength), the amplitude of movements in the knee joint (goniometry) and the visual analog pain scale (VAS) on the 14th day, 1.5 months, 3 and 5 months after the operation. This part of the study showed the advantages of the developed rehabilitation program using elements of kinesiotaping, as only a few patients with functional disorders were found in OG while in the comparison group their number was up to 20%. Improvement of joint function and normalization of muscle strength and goniometry indicators occurred earlier in OG patients by 2 weeks, compared to patients who underwent restorative treatment according to the traditional method of the city polyclinic.
 A special place in the assessment of results is given to determining the quality of life using the SF-36 questionnaire. The dynamics of quality of life indicators showed a gradual and likely improvement of all components of quality of life at the entire stage of post-hospital rehabilitation. We proved that the proposed rehabilitation program is more effective compared to the traditional methods of restorative treatment of a medical institution and allows achieving better results in restoring the functions of the knee joint in the shortest possible time after the injury and can be recommended for wide use.

In utero Exposure to Valproic Acid throughout Pregnancy Causes Phenotypes of Autism in Offspring Mice

Valproic acid (VPA) is an antiepileptic drug that inhibits the epileptic activity of neurons mainly by inhibiting sodium channels and GABA transaminase. VPA is also known to inhibit histone deacetylases, which epigenetically modify the cell proliferation/differentiation characteristics of stem/progenitor cells within developing tissues. Recent clinical studies in humans have indicated that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in offspring; we have previously reported that low-dose VPA exposure in utero throughout pregnancy increases the production of projection neurons from neuronal stem/progenitor cells that are distributed in the superficial neocortical layers of the fetal brain. In the present study, we found that in utero VPA-exposed mice exhibited abnormal social interaction, changes in cognitive function, hypersensitivity to pain/heat, and impaired locomotor activity, all of which are characteristic symptoms of autism spectrum disorder in humans. Taken together, our findings indicate that VPA exposure in utero throughout pregnancy alters higher brain function and predisposes individuals to phenotypes that resemble autism and intellectual disability. Furthermore, these symptoms are likely to be due to neocortical dysgenesis that was caused by an increased number of projection neurons in specific layers of the neocortex.

Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS

The gut microbiome is a potential non-genetic contributing factor for Amyotrophic Lateral Sclerosis. Differences in gut microbial communities have been detected between ALS subjects and healthy controls, including an increase in Escherichia coli in ALS subjects. E. coli and other gram-negative bacteria produce curli proteins, which are functional bacterial amyloids. We examined whether long-term curli overexposure in the gut can exacerbate the development and progression of ALS. We utilized the slow-developing hSOD1-G93A mouse model of ALS with their C57BL/6J WT littermate controls, including males and females, with a total of 91 animals. These mice were on a normal chow diet and fed curli-producing or curli-nonproducing (mutant) E. coli in applesauce (vehicle) 3 times/week, from 1 through 7 months of age. Male hSOD1 mice demonstrated gradual slowing in running speed month 4 onwards, while females exhibited no signs of locomotive impairment even at 7 months of age. Around the same time, male hSOD1 mice showed a gradual increase in frequency of peripheral CD19+ B cells. Among the male hSOD1 group, chronic gut exposure to curli-producing E. coli led to significant shifts in α- and β-diversities. Curli-exposed males showed suppression of immune responses in circulation, but an increase in markers of inflammation, autophagy and protein turnover in skeletal muscle. Some of these markers were also changed in mutant E. coli-exposed mice, including astrogliosis in the brainstem and demyelination in the lumbar spinal cord. Overall, chronic overexposure to a commensal bacteria like E. coli led to distant organ pathology in our model, without the presence of a leaky gut at 6 months. Mechanisms underlying gut-distant organ communication are of tremendous interest to all disciplines.

Exploring Temporospatial Gait Asymmetry, Dynamic Balance, and Locomotor Capacity After a 12-Week Split-Belt Treadmill Training in Adolescents with Unilateral Cerebral Palsy: A Randomized Clinical Study

Aim To investigate the effects of a 12-week split-belt treadmill walking (Sb-TW) practice using an error augmentation strategy on temporospatial gait asymmetries, dynamic balance, and locomotor capacity in adolescents with unilateral cerebral palsy (ULCP). Methods Fifty-two adolescents with ULCP (age: 10–16 years) were randomized into either the Sb-TW group (n = 26; underwent repeated Sb-TW practice, with exaggeration of the initial step-length asymmetry, three times/week, for 12 sequential weeks) or control group (n = 26; received equivalent dosages of traditional single-belt treadmill training). Step-length and swing-time asymmetries, directional (LoSdirectional) and overall (LoSoverall) limits of stability, and locomotor capacity [6-minute walk test (6-MWT), Timed Up and Down Stair test (TUDS), and 10-m Shuttle Run Test (10mSRT)] were assessed pre- and post-intervention. Results The Sb-TW group demonstrated more favorable changes in step-length asymmetry (p < .001, η 2 partial = 0.27), LoSdirectional [affected side direction (p = .033, η 2 partial = 0.09), forward direction (p = .004, η 2 partial = 0.16), and backward direction (p = .01, η 2 partial = 0.12)], and LoSoverall (p < .001, η 2 partial = 0.31) than the control group. Also, the Sb-TW group showed significantly higher locomotor capacity [6-MWT (p < .001, η 2 partial = 0.38), TUDS (p = .032, η 2 partial = 0.09), 10mSRT (p = .021, η 2 partial = 0.10)] as compared to the control group. Conclusion The Sb-TW-induced adaptations can be capitalized on for remediating spatial gait asymmetry, dynamic balance deficits, and impaired locomotor performance in adolescents with ULCP.

Toxicological evaluation of zidovudine and novel chalcogen derivatives in Drosophila melanogaster.

Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 μM impaired flies'locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno-phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p-methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates.

Neonatal treatment with fluoxetine alters locomotor activity and the cortical glial/neuron index in rats with cerebral palsy.

Cerebral palsy (CP) is characterized by motor disorders, including deficits in locomotor activity, coordination, and balance. Selective serotonin reuptake inhibitors have been shown to play an important role in brain plasticity. This study investigates the effect of neonatal treatment using fluoxetine on locomotor activity and histomorphometric parameters of the primary somatosensory cortex (S1) in rats submitted to an experimental model of CP. CP was found to reduce bodyweight and locomotion parameters and also to increase the glia/neuron index in the S1. Administration of fluoxetine 10mg/kg reduced bodyweight, impaired locomotor activity parameters, and increased the number of glial cells and the glia/neuron ratio in the S1 in rats with CP. However, treatment with fluoxetine 5mg/kg was not found to be associated with adverse effects on locomotor activity and seems to improve histomorphometric parameters by way of minor changes in the S1 in animals with CP. These results thus indicate that experimental CP, in combination with the use of a high dose of fluoxetine (10mg/kg), impairs locomotor and histomorphometric parameters in the S1, while treatment with a low dose of fluoxetine (5mg/kg) averts the negative outcomes associated with a high dose of fluoxetine in relation to these parameters but produces no protective effect.

Blocking prokineticin receptors attenuates synovitis and joint destruction in collagen-induced arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated by an interdependent network of proinflammatory molecules such as chemokines. Prokineticin 2 (PK2) is a chemokine-like peptide that modulates nociceptive threshold and immuno-inflammatory processes via two G-protein-linked receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2). In the present study, we investigated the effects of the prokineticin receptor antagonist PC1 on arthritic pain and the inflammatory response in type II collagen-induced arthritis (CIA) in mice. We demonstrated that PC1, administered subcutaneously from day 25 to day 35 after CIA, improved clinical signs of arthritis such as paw edema, pain, and impaired locomotor activity. In CIA mice, PC1 was also able to lower plasma malondialdehyde (MDA) levels, suggesting a role in reducing oxidative damage, as well as joint expression levels of PK2, PKRs, TNFα, IL-1β, CD4, CD8, and NF-kB. These results suggest that blocking PKRs may be a successful strategy to control arthritic pain and pathology development. KEY MESSAGES: PK2/PKRs expression levels strongly increase in the synovium of RA mice. PC1 treatment shows anti-arthritic activity and reduces arthritis-induced pain. PC1 treatment significantly lowers synovial PK2/PKRs levels. PC1 treatment lowers plasma MDA levels and synovial levels of TNFα and IL -1β PC1 treatment is a viable therapeutic option for RA.