Coordination Deficits Research Articles

Access to and Transitions within the Medical Care Process of Persons with Down Syndrome and Dementia: A Qualitative Analysis

Compared to the general population, individuals with Down syndrome carry a much higher genetic risk of developing early onset Alzheimer's dementia. This leads to unique challenges and the need for a targeted patient journey.In a qualitative interview study with medical professionals, patient organisations and formal and informal care persons, we assessed barriers within the medical care process of this patient group as well as current approaches to overcome these problems. The study is one module of a multi-method project founded by the Innovation Fund of the German Joint Commission. The results presented here focus on access to and transitions within the medical care process. 14 guided interviews were conducted by a team of moderators by video conference, recorded and transcribed. The analysis of the results was carried out as a qualitative content analysis based on the methods of Mayring.Given the varying degree of premorbid intellectual disability, difficulties recognizing dementia symptoms were reported leading to delays in initiating the diagnostic process. Limited knowledge of the special disease risk and symptom manifestation in routine medical care as well as the lack of specialized medical institutions were identified as additional hurdles. Insufficient dissemination of information about existing specialised institutions to regular physicians and caregivers was criticized. All stakeholder groups drew attention to limitations in access to occupational and speech therapy because of the inadequate number of specialized therapists. Improvements suggested by the interview partners focussed on topics such as the implementation of guidance of the patient journey to and within the medical care process by one institution, easily accessible information for patients and caregivers as well as optimised training for physicians in routine care.Barriers such as insufficient availability of specialised service providers and information deficits about the specific disease risks and symptoms of the population have also been identified in international literatur; in addition, management and coordination deficits in the fragmented German health care system represent well known additional barriers. Approaches to improve the situation can be seen, on the one hand, in improved information and training offers for caregivers and service providers, and, on the other hand, in the expansion of the range of specialized service providers, in particular the Medical Centres for Adults with Disabilities. Informed by these study results and the results of other project modules, health policy recommendations for the improvement of the patient journey of patients with Down syndrome and dementia will be developed in the last project module.

CXCR2 immunomodulatory therapy protects against microstructural white matter injury and gait abnormalities but does not mitigate deficits of cognition in a preclinical model of cerebral palsy.

Minimizing central nervous system (CNS) injury from preterm birth depends upon understanding the critical pathways that underlie essential neurodevelopmental and CNS pathophysiology. Signaling by chemokine (C-X-C motif) ligand 1 (CXCL1) through its cognate receptor, CXCR2 [(C-X-C motif) receptor 2] is essential for neurodevelopment. Increased CXCR2 signaling, however, is implicated in a variety of uterine and neuropathologies, and their role in the CNS injury associated with perinatal brain injury is poorly defined. To evaluate the long-term efficacy of CXCR2 blockade in functional repair of brain injury secondary to chorioamnionitis (CHORIO), we used an established preclinical rat model of cerebral palsy. We tested the hypothesis that transient postnatal CXCR2 antagonism with SB225002 would reduce gait deficits, hypermobility, hyperactivity, and disinhibition concomitant with repair of functional and anatomical white and gray matter injury. CHORIO was induced in pregnant Sprague Dawley rats on embryonic day 18 (E18). SB225002 (3 mg/kg) was administered intraperitoneally from postnatal day 1 (P1)-P5. Rats were aged to adulthood and tested for gait, open-field behavior and cognitive and executive function deficits using a touchscreen cognitive assessment platform. Results show that transient CXCR2 blockade attenuated microstructural white matter injury after CHORIO consistent with improved anatomical connectivity, and mitigated deficits in gait coordination, posture, balance, paw placement, and stepping (p < 0.05). Animals with CHORIO were hyperactive and hypermobile with fMRI deficits in neural circuitry central to cognition. However, CXCR2 antagonism in CHORIO animals did not normalize open-field behavior, neural activity, or cognition on a touchscreen task of discrimination learning (all p > 0.05). Studies in CXCR2 knockout mice confirmed significantly impaired cognitive performance independent of CHORIO. Taken together, transient postnatal blockade of CXCR2 ameliorates aspects of the lasting neural injury after CHORIO including normalizing gait deficits and white matter injury. However, improvement in essential functional and cognitive domains are not achieved limiting the utility of this therapeutic approach for treatment of perinatal brain injury. This study emphasizes the complex, multi-faceted role of chemokines in typical neurodevelopment, circuit formation, neural network function, and injury response.

Distinctive features of bimanual coordination in idiopathic normal pressure hydrocephalus

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is characterized by cerebrospinal fluid circulation disorders, and presents as gait and balance disturbances similar to those observed in other incurable neurological diseases. Although previous studies have reported deficits in bimanual coordination among patients with iNPH, these potential pathological characteristics have not received much attention to date. This study investigated the temporal characteristics of a bimanual finger-tapping task in patients with iNPH, focusing on within- and between-hand coordination.MethodsStudy participants comprised three groups: patients with iNPH (N = 19, mean age = 76.9 ± 5.6 years), older adults (N = 19, 76.4 ± 5.3 years), and younger adults (N = 13, 32.2 ± 8.5 years). Participants performed a bimanual finger-tapping task under five conditions that manipulated the temporal differences between the two taps.ResultsThe iNPH group exhibited significantly greater errors in both within- and between-hand coordination tasks compared to the other two groups.ConclusionThese results suggest that assessing temporal errors in bimanual coordination tasks, particularly within-hand coordination, may be useful for uncovering pathological characteristics specific to iNPH.

Return to Sports After Arthroplasty

Arthroplasty of the hip has become one of the most successful surgical interventions and has seen significant advancements over the last century. With these developments, patient expectations have shifted from merely achieving pain-free daily mobility to anticipating a full recovery, including the ability to participate in sports. This shift has driven innovations in prosthetic materials and surgical techniques, such as the development of wear-resistant materials like highly cross-linked polyethylene and the adoption of minimally invasive procedures to enhance recovery.However, concerns persist among patients about the risks of resuming sports postoperatively, particularly the fear of prosthesis-related accidents or failures. A survey of 300 German surgeons identified periprosthetic fractures as the greatest risk, followed by polyethylene wear and implant loosening. The study also examines osteoporosis as a risk factor, suggesting that while sports can help prevent periprosthetic osteoporosis, high-energy trauma may increase the severity of injuries. Although modern prosthetic materials have reduced wear and improved durability, the type and intensity of physical activity continue to influence prosthesis longevity.Therefore, it is recommended that low-impact sports be resumed 3-6 months postoperatively, while high-impact sports should be approached with caution, particularly during the first year after surgery, to minimize the risk of complications. Coordination training before and after surgery is also emphasized to reduce the risk of falls and injuries. In summary, the study highlights that high-impact sports cannot be generally recommended, as coordination deficits may persist for up to 12 months following total hip replacement. Such activities should only be considered later-on and only by patients who are experienced in these specific sports.

NCOG-11. FACTORS PREDICTING SPEECH AND GAIT RECOVERY IN CHILDREN WITH POST-OPERATIVE POSTERIOR FOSSA SYNDROME (PFS)

Abstract Posterior fossa syndrome/cerebellar mutism syndrome is a surgical complication of posterior fossa tumor resection, especially midline tumors. Initially thought to involve complete mutism, PFS is now recognized as a complex syndrome involving loss of language (complete [PFS1] and incomplete [PFS2]). Additional symptoms include apraxia, movement disorder, motor and coordination deficits, and emotional lability. The aim of this study was to identify factors that influence delayed speech and independent gait recovery in children with PFS. We prospectively studied 73 children ≥3 years of age with medulloblastoma who developed PFS (SJMB12, NCT01878617). Enrolled children received standardized neurologic examinations and serial imaging before, during and up to five years after completion of therapy. Neurological examinations included scale for assessment and rating of ataxia (SARA), CTCAE grading of neurologic deficits, and severity of injury to the superior cerebellar peduncles (SCP) on post-operative MRI. Median time to speech recovery was 1.4 months (range 0.3-14.3); 81% had return of speech at 3 months and 97% at 12 months. On multivariable Cox regression analysis, complete mutism (HR 0.17, p&amp;lt;0.0001) and inability to sit (HR 0.40, p=0.001) were associated with delayed speech return. Independent ambulation was regained by 80.8% at a median of 2.3 (range 0.3-71.3) months. 70% had a return of ambulation at 12 months and 77% at 24 months. On multivariable Cox regression analysis, complete mutism (HR 0.32, p=0.016), inability to sit (HR 0.30, p=0.002), SARA score (HR 0.94, p=0.002), and right SCP injury (HR 0.47, p=0.014) were significantly associated with delayed return of ambulation. Presence of mutism, inability to sit unassisted, higher SARA score, and right SCP injury at the time of PFS diagnosis are associated with time to recovery of speech/language and ambulation. Our findings have prognostic implications for families and to help identify children in need of more intensive interventions.

Effects of Baduanjin on motor function in children with developmental coordination disorders: study protocol for a randomised controlled trial

IntroductionChildren diagnosed with developmental coordination disorder (DCD) exhibit a range of challenges in both gross and fine motor skills, characterised by sluggish and awkward movements. Additionally, they experience deficits in...

Clinical coordination in cancer diagnosis: healthcare stakeholders’ viewpoints in Latin America

Abstract Background Delays in diagnosis contribute to increasing cancer mortality rates in Latin American countries due to, among others, highly fragmented healthcare systems. The objective of this study, part of a larger research project (EquityCancer-LA), was to analyze cross-level coordination during cancer diagnosis and factors influencing it from healthcare stakeholders’ perspectives in Chile, Colombia, and Ecuador. Methods This descriptive-interpretative qualitative study was based on 114 semi-structured individual interviews in 2022-23 using a criterion sample of health professionals from primary care (PC) (n = 40) and secondary care (SC) (n = 44) as well as managers and policy makers (n = 30) from two public healthcare networks in each country. Sample reached saturation. A thematic analysis was conducted first by country and then comparatively, guided by the theoretical framework of clinical coordination. Results In all countries, informants highlighted limited cross-level exchange of information and limited coordination of clinical management, delays in referral, and long waiting times after referral, leading to diagnostic delays. Factors hindering coordination differed across countries: structural (insufficient personnel, access to diagnostic tests in PC); organizational (limited/inadequate coordination mechanisms, e.g. shared clinical records; poor working conditions); and health professional characteristics (limited knowledge and skills among PC doctors). Direct feedback was emphasized to facilitate coordination of cancer diagnosis: virtual joint clinical conferences in Chile, co-location of PC and SC in Colombia, and informal networks (based on personal contacts) in Ecuador. Conclusions The findings underscore the critical coordination problems contributing to delays in cancer diagnosis. Addressing these challenges requires strategic interventions aimed at strengthening primary care and fostering cross-level coordination. Key messages • Cancer diagnosis in Latin America suffers from coordination deficits due to structural, organizational, and professional factors. • Strengthening primary care and cross-level coordination is needed.

MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination.

Muscleblind-like proteins (MBNLs) are a family of RNA-binding proteins that play essential roles in the regulation of RNA metabolism. Beyond their canonical role in RNA regulation, MBNL proteins have emerged as key players in the pathogenesis of Myotonic Dystrophy type 1 (DM1). In DM1, sequestration of MBNL proteins by expansion of the CUG repeat RNA leads to functional depletion of MBNL, resulting in deregulated alternative splicing and aberrant RNA processing, which underlie the clinical features of the disease. While attention to MBNL proteins has focused on their functions in skeletal muscle, new evidence suggests that their importance extends to motor neurons (MNs), pivotal cellular components in the control of motor skills and movement. To address this question, we generated conditional double knockout mice in which Mbnl1 and Mbnl2 were specifically deleted in motor neurons (MN-dKO). Adult MN-dKO mice develop gait coordination deficits associated with structural and ultrastructural defects in the neuromuscular junction, indicating that MBNL activity in MNs is crucial for the maintenance of the neuromuscular junction. In addition, transcriptome analysis performed on the spinal cord of MN-dKO mice identified mis-splicing events in genes associated with synaptic transmission and neuromuscular junction homeostasis. In summary, our results highlight the complex roles and regulatory mechanisms of MBNL proteins in MNs for muscle function and locomotion. This work provides valuable insights into fundamental aspects of RNA biology and offers promising avenues for therapeutic intervention in DM1 as well as a range of diseases associated with RNA dysregulation.

In Vivo Expression of an SCA27A-linked FGF14 Mutation Results in Haploinsufficiency and Impaired Firing of Cerebellar Purkinje Neurons.

Autosomal dominant mutations in FGF14 , which encodes intracellular fibroblast growth factor 14 (iFGF14), underlie spinocerebellar ataxia type 27A (SCA27A), a devastating multisystem disorder resulting in progressive deficits in motor coordination and cognitive function. Mice lacking iFGF14 ( Fgf14 -/- ) exhibit similar phenotypes, which have been linked to iFGF14-mediated modulation of the voltage-gated sodium (Nav) channels that control the high frequency repetitive firing of Purkinje neurons, the main output neurons of the cerebellar cortex. To investigate the pathophysiological mechanisms underlying SCA27A, we developed a targeted knock-in strategy to introduce the first point mutation identified in FGF14 into the mouse Fgf14 locus ( Fgf14 F145S ), we determined the impact of in vivo expression of the mutant Fgf14 F145S allele on the motor performance of adult animals and on the firing properties of mature Purkinje neurons in acute cerebellar slices. Electrophysiological experiments revealed that repetitive firing rates are attenuated in adult Fgf14 F145S/+ cerebellar Purkinje neurons, attributed to a hyperpolarizing shift in the voltage-dependence of steady-state inactivation of Nav channels. More severe effects on firing properties and Nav channel inactivation were observed in homozygous Fgf14 F145S/F145S Purkinje neurons. Interestingly, the electrophysiological phenotypes identified in adult Fgf14 F145S/+ and Fgf14 F145S/F145S cerebellar Purkinje neurons mirror those observed in heterozygous Fgf14 +/- and homozygous Fgf14 -/- Purkinje neurons, respectively, suggesting that the mutation results in the loss of the iFGF14 protein. Western blot analysis of lysates from adult heterozygous Fgf14 F145S/+ and homozygous Fgf14 F145S/F145S animals revealed reduced or undetectable, respectively, iFGF14 expression, supporting the hypothesis that the mutant allele results in loss of the iFGF14 protein and that haploinsufficiency underlies SCA27A neurological phenotypes.

Human motor learning dynamics in high-dimensional tasks.

Conventional approaches to enhance movement coordination, such as providing instructions and visual feedback, are often inadequate in complex motor tasks with multiple degrees of freedom (DoFs). To effectively address coordination deficits in such complex motor systems, it becomes imperative to develop interventions grounded in a model of human motor learning; however, modeling such learning processes is challenging due to the large DoFs. In this paper, we present a computational motor learning model that leverages the concept of motor synergies to extract low-dimensional learning representations in the high-dimensional motor space and the internal model theory of motor control to capture both fast and slow motor learning processes. We establish the model's convergence properties and validate it using data from a target capture game played by human participants. We study the influence of model parameters on several motor learning trade-offs such as speed-accuracy, exploration-exploitation, satisficing, and flexibility-performance, and show that the human motor learning system tunes these parameters to optimize learning and various output performance metrics.

Knockout of neutrophil cytosolic factor 1 ameliorates neuroinflammation and motor deficit after traumatic brain injury

Traumatic brain injury (TBI) is a predominant cause of long-term disability in adults, yet the molecular mechanisms underpinning the neuropathological processes associated with it remain inadequately understood. Neutrophil cytosolic factor 1 (NCF1, also known as p47phox) is one of the cytosolic components of NADPH oxidase NOX2. In this study, we observed a reduction in the volume of TBI-induced brain lesions in NCF1-knockout mice compared to controls. Correspondingly, the neuronal loss induced by TBI was mitigated in the NCF1-knockout mice. Behavioral analysis also demonstrated that the motor coordination deficit following TBI was mitigated by the depletion of NCF1. Mechanistically, our findings revealed that NCF1 deficiency attenuated TBI-induced inflammatory responses by inhibiting the release of proinflammatory factors and reducing neutrophil infiltration into the brain parenchyma. Additionally, our results indicated that NCF1 deficiency significantly decreased the levels of reactive oxygen species in neutrophils. Taken together, our findings indicate that NCF1 plays a crucial role in the regulation of brain injury and secondary inflammation post-TBI.

Boosting Serotonin Synthesis Is Not Sufficient to Improve Motor Coordination of Mecp2 Heterozygous Mouse Model of Rett Syndrome.

Motor deficit is a core symptom of Rett syndrome, a rare neurological disease caused in most cases by mutations of the methyl-CpG-binding protein2 (MECP2) gene. Serotonin reuptake inhibitors improve motor coordination in Mecp2 heterozygous (Het) mice and serotonin depletion prevented this effect. Here, we assess alterations in indole levels in various brain regions and whether boosting brain serotonin synthesis with the serotonin precursors tryptophan, 5-hydroxytryptophan and α-lactalbumin rescued motor coordination deficit of Mecp2 Het mice. Motor coordination was assessed in the accelerated rotarod during and after systemic administration of serotonin precursors for 2-3 weeks. Since no data are available, the effect of α-lactalbumin on tryptophan, serotonin and 5-hydroxyindoleacetic acid levels was evaluated in various brain regions in order to identify the dose of ALAC to evaluate on motor coordination. As compared to WT, Mecp2 Het mice show reduced levels of serotonin in the whole brain, hippocampus, brainstem and cerebral cortex, but not the striatum. Reduced levels of 5-hydroxyindoleacetic acid were observed in the hippocampus and brainstem. Doses of serotonin precursors increasing brain tryptophan and/or serotonin production and metabolism had no effect on motor coordination. The results indicate that boosting serotonin synthesis is not sufficient to improve motor coordination of Mecp2 Het mice.

Aberrant copper metabolism and hepatic inflammation cause neurological manifestations in a mouse model of Wilson’s disease

Pathogenic germline mutations in the P-type copper-transporting ATPase (ATP7B) gene cause Wilson’s disease (WD), a hereditary disorder characterized by disrupted copper metabolism. The Arg778Leu (R778L) mutation in exon 8 is prevalent among individuals with WD in East Asia and is associated with more severe phenotypes. In this study, we generated a WD mouse model harboring R778L mutation (R778L mice) using CRISPR/Cas9. R778L mice exhibit a range of pathological characteristics resembling those of patients with WD and the same point mutations, including aberrant copper metabolism, pathological cellular injury, inflammation, and severe hepatic fibrosis. At 3–5 months of age, these mice started to display neurological deficits in motor coordination and cognitive dysfunction, accompanied by increased expression of inflammatory cytokines in the central nervous system. Microglia in the striatum and cortex exhibit significant activation, shorter processes, and decreased branch points. However, the Cu2+ levels in the brain tissue of R778L mice did not differ significantly from those of wild-type mice. Notably, inhibition of hepatic inflammation with PJ34 or siNfkb markedly alleviated the deficiencies in cognitive performance and improved locomotor activity in R778L mice. Thus, this study establishes a novel murine model to investigate the pathophysiology of WD, highlights the liver-brain crosstalk responsible for neurological manifestations in individuals with WD caused by the R778L point mutation, and demonstrates the potential of modulating liver inflammation as a therapeutic strategy for alleviating the neurological manifestations of WD.

Cognitive behavioral phenotyping of DSCAM heterozygosity as a model for autism spectrum disorder.

It is estimated that 1 in 36 children are affected by autism spectrum disorder (ASD) in the United States, which is nearly a twofold increase from a decade ago. Recent genetic studies have identified de novo loss-of-function (dnLoF) mutations in the Down Syndrome Cell Adhesion Molecule (DSCAM) as a strong risk factor for ASD. Previous research has shown that DSCAM ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent DSCAM underexpression captures the full range of behaviors, specifically cognitive phenotypes, presented in ASD. Here, we conducted a comprehensive cognitive behavioral phenotyping which revealed that loss of one copy of DSCAM, as in the DSCAM2J+/-, that is, DSCAM heterozygous mice, displayed hyperactivity, increased anxiety-like behavior, and motor coordination deficits. Additionally, hippocampal-dependent learning and memory was affected, including impairments in working memory, long-term memory, and contextual fear learning. Interestingly, implicit learning processes remained intact. Therefore, DSCAM LoF produces autistic-like behaviors that are similar to those observed in human cases of ASD. These findings further support a role for DSCAM dnLoF mutations in ASD and suggest DSCAM2J+/- as a suitable model for ASD research.

Selective deletion of Tsc1 from mouse cerebellar Purkinje neurons drives sex-specific behavioral impairments linked to autism.

There is a striking sex bias in the prevalence and severity of autism spectrum disorder (ASD) with 80% of diagnoses occurring in males. Because the molecular etiology of ASD is likely combinatorial, including interactions across multiple genetic and environmental factors, it is difficult to investigate the physiological mechanisms driving sex-specific differences. Loss of function mutations in TSC1 result in dysregulated mTORC1 signaling and underlie a multi-system disorder known as tuberous sclerosis (TSC). Interestingly, more than 50% of individuals diagnosed with TSC are also diagnosed with ASD, making TSC mutations one of the most prevalent monogenic causes of ASD. Mice harboring targeted deletion of Tsc1 selectively in cerebellar Purkinje neurons, referred to here as Tsc1 mut/mut , have multiple ASD-linked behavioral impairments, including deficits in social interactions, motor coordination, and vocalizations. However, these ASD-linked behavioral deficits have only been investigated using male Tsc1 mut/mut animals. Here, we used cohorts of male and female Tsc1 mut/mut animals to determine if behavioral impairments, previously identified in this model, are similar across sex. Specifically, we measured balance and motor coordination and social interaction behaviors in two age groups across sex. W e determined balance and motor coordination deficits are similar in male and female Tsc1 mut/mut mice, and that deficits in the firing of Tsc1 mut/mut Purkinje neurons located in the cerebellar vermis are also similar across sex. However, impairments in social approach behavior were found to be significantly more severe in Tsc1 mut/mut males compared to females. These results indicate the selective deletion of Tsc1 in Purkinje neurons differentially impairs cerebellar circuits based on sex.

Sew and Tell: A Descriptive Examination of the Occupation of Sewing for Adults

Abstract Date Presented 03/22/24 Sewing as an occupation-based intervention was found to be effective in increasing social participation, occupational performance, and quality of life for adults with conditions affecting fine motor coordination and cognitive deficits. Primary Author and Speaker: Camille Skubik-Peplaski Additional Authors and Speakers: Jose Gonzalez, Susan Skees Hermes, Amanda S Hansford

Structured neurological soft signs examination reveals motor coordination deficits in adults diagnosed with high-functioning autism

Neurological soft signs (NSS), discrete deficits in motor coordination and sensory integration, have shown promise as markers in autism diagnosis. While motor impairments, partly associated with core behavioral features, are frequently found in children with autism, there is limited evidence in adults. In this study, NSS were assessed in adults undergoing initial diagnosis of high-functioning autism (HFA), a subgroup difficult to diagnose due to social adaptation and psychiatric comorbidity. Adults with HFA (n = 34) and 1:1 sex-, age-, and intelligence-matched neurotypical controls were administered a structured NSS examination including motor, sensory, and visuospatial tasks. We showed that adults with HFA have significantly increased motor coordination deficits compared with controls. Using hierarchical cluster analysis within the HFA group, we also identified a subgroup that was particularly highly affected by NSS. This subgroup differed from the less affected by intelligence level, but not severity of autism behavioral features nor global psychological distress. It remains questionable whether motor impairment represents a genuinely autistic trait or is more a consequence of factors such as intelligence. Nevertheless, we conclude that examining NSS in terms of motor coordination may help diagnose adults with HFA and identify HFA individuals who might benefit from motor skills interventions.

Exploring the incidence of balance and coordination deficits amongst obese adolescents attending school: Insights from an online cross-sectional survey

ABSTRACT Background: Balance is maintained through automatic postural adjustments that ensure stability during various activities. Developmental Coordination Disorder (DCD) is often associated with other developmental issues, such as attention-deficit hyperactivity disorder (ADHD), learning disabilities, speech-language delays, and behavioral and emotional difficulties. Body mass index (BMI) for age is widely used in clinical and public health settings to determine whether a child or adolescent is overweight or obese. Aims: This study aimed to systematically examine the prevalence of balance and coordination impairments among obese adolescents attending school. Materials and Methods: A cross-sectional survey was conducted on a sample of 368 school-going obese adolescents. A self-developed questionnaire assessing balance and coordination was administered to the participants. The BMI was calculated for each participant to confirm obesity status. Results: The study found a significant prevalence of balance and coordination impairments among the obese school-going adolescents surveyed. These impairments were observed across various activities requiring postural adjustments and motor skills. Conclusions: The findings suggest a notable incidence of balance and coordination deficits in obese adolescents, highlighting the need for targeted interventions in this population to address these motor skill challenges.

Impaired memory in Sprague-Dawley rats exposed to complex groundwater mixtures of contaminants is associated with reduced cranial blood flow and hippocampal neurotoxicity

Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10 % v/v low impact groundwater, and (iii) 0.01 %, 0.1 %, 1 %, and 10 % high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.

Chronic Treatment with Oxcarbazepine Attenuates Its Anticonvulsant Effect in the Maximal Electroshock Model in Mice.

The objective of this study was to assess the impact of acute and chronic treatment with oxcarbazepine on its anticonvulsant activity, neurological adverse effects, and protective index in mice. Oxcarbazepine was administered in four protocols: once or twice daily for one week (7 × 1 or 7 × 2) and once or twice daily for two weeks (14 × 1 or 14 × 2). A single dose of the drug was employed as a control. The anticonvulsant effect was evaluated in the maximal electroshock test in mice. Motor and long-term memory impairment were assessed using the chimney test and the passive avoidance task, respectively. The concentrations of oxcarbazepine in the brain and plasma were determined via high-performance liquid chromatography. Two weeks of oxcarbazepine treatment resulted in a significant reduction in the anticonvulsant (in the 14 × 1; 14 × 2 protocols) and neurotoxic (in the 14 × 2 schedule) effects of this drug. In contrast, the protective index for oxcarbazepine in the 14 × 2 protocol was found to be lower than that calculated for the control. No significant deficits in memory or motor coordination were observed following repeated administration of oxcarbazepine. The plasma and brain concentrations of this anticonvulsant were found to be significantly higher in the one-week protocols. Chronic treatment with oxcarbazepine may result in the development of tolerance to its anticonvulsant and neurotoxic effects, which appears to be dependent on pharmacodynamic mechanisms.