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Saudi Journal of Biological Sciences Jun 2023The examination was sighted to study the preventive effects of rosinidin against rotenone-activated Parkinson's disease in rats.
OBJECTIVES
The examination was sighted to study the preventive effects of rosinidin against rotenone-activated Parkinson's disease in rats.
METHODS
Animals were randamoized into five groups: I-saline, II-rotenone (0.5 mg/kg/b.wt.), III- IV-10 and 20 mg/kg rosinidin after rotenone and V-20 mg/kg rosinidin per se for 28 days and were assigned for behavioral analysis., Biochemical parameters i.e. lipid peroxidation, endogenous antioxidants, nitrite level, neurotransmitter levels, proinflammatory biomarkers such as interleukin- 6 (IL-6), tumor necrosis factor-α, IL-1β, nuclear factor kappa B, nuclear factor erythroid 2-related factor 2, and caspase-3 were assessed on the 29th day of the research.
RESULTS
Rosinidin augmented the effectiveness of rotenone on akinesia, catalepsy, forced-swim test, rotarod, and open-field test. Biochemical findings indicated that treatment of rosinidin showed restoring neuroinflammatory cytokines, antioxidants, and neurotransmitter levels in rotenone-injected rats.
CONCLUSION
As a result of rosinidin treatment, the brain was protected from oxidative stress-induced neuronal damage and inhibited neuroinflammatory cytokines.
PubMed: 37187936
DOI: 10.1016/j.sjbs.2023.103656 -
International Journal of Molecular... Apr 2023Excessive inhibition of the external globus pallidus (GPe) by striatal GABAergic neurons is considered a central mechanism contributing to motor symptoms of Parkinson's...
Excessive inhibition of the external globus pallidus (GPe) by striatal GABAergic neurons is considered a central mechanism contributing to motor symptoms of Parkinson's disease (PD). While electrophysiological findings support this view, behavioral studies assessing the beneficial effects of global GPe activations are scarce and the reported results are controversial. We used an optogenetic approach and the standard unilateral 6-hydroxydopamine nigrostriatal dopamine (DA) lesion model of PD to explore the effects of GPe photostimulation on motor deficits in mice. Global optogenetic GPe inhibition was used in normal mice to verify whether it reproduced the typical motor impairment induced by DA lesions. GPe activation improved ipsilateral circling, contralateral forelimb akinesia, locomotor hypoactivity, and bradykinesia in 6-OHDA-lesioned mice at ineffective photostimulation parameters (532 nm, 5 Hz, 3 mW) in normal mice. GPe photoinhibition (450 nm, 12 mW) had no effect on locomotor activity and forelimb use in normal mice. Bilateral photoinhibition (450 nm, 6 mW/side) reduced directed exploration and improved working memory performances indicating that recruitment of GPe in physiological conditions may depend on the behavioral task involved. Collectively, these findings shed new light on the functional role of GPe and suggest that it is a promising target for neuromodulatory restoration of motor deficits in PD.
Topics: Mice; Animals; Parkinson Disease; Globus Pallidus; Oxidopamine; Optogenetics; Corpus Striatum; Dopamine; Hypokinesia
PubMed: 37175643
DOI: 10.3390/ijms24097935 -
Journal of Neuroengineering and... Apr 2023Freezing of gait (FOG) is an unpredictable gait arrest that hampers the lives of 40% of people with Parkinson's disease. Because the symptom is heterogeneous in...
BACKGROUND
Freezing of gait (FOG) is an unpredictable gait arrest that hampers the lives of 40% of people with Parkinson's disease. Because the symptom is heterogeneous in phenotypical presentation (it can present as trembling/shuffling, or akinesia) and manifests during various circumstances (it can be triggered by e.g. turning, passing doors, and dual-tasking), it is particularly difficult to detect with motion sensors. The freezing index (FI) is one of the most frequently used accelerometer-based methods for FOG detection. However, it might not adequately distinguish FOG from voluntary stops, certainly for the akinetic type of FOG. Interestingly, a previous study showed that heart rate signals could distinguish FOG from stopping and turning movements. This study aimed to investigate for which phenotypes and evoking circumstances the FI and heart rate might provide reliable signals for FOG detection.
METHODS
Sixteen people with Parkinson's disease and daily freezing completed a gait trajectory designed to provoke FOG including turns, narrow passages, starting, and stopping, with and without a cognitive or motor dual-task. We compared the FI and heart rate of 378 FOG events to baseline levels, and to stopping and normal gait events (i.e. turns and narrow passages without FOG) using mixed-effects models. We specifically evaluated the influence of different types of FOG (trembling vs akinesia) and triggering situations (turning vs narrow passages; no dual-task vs cognitive dual-task vs motor dual-task) on both outcome measures.
RESULTS
The FI increased significantly during trembling and akinetic FOG, but increased similarly during stopping and was therefore not significantly different from FOG. In contrast, heart rate change during FOG was for all types and during all triggering situations statistically different from stopping, but not from normal gait events.
CONCLUSION
When the power in the locomotion band (0.5-3 Hz) decreases, the FI increases and is unable to specify whether a stop is voluntary or involuntary (i.e. trembling or akinetic FOG). In contrast, the heart rate can reveal whether there is the intention to move, thus distinguishing FOG from stopping. We suggest that the combination of a motion sensor and a heart rate monitor may be promising for future FOG detection.
Topics: Humans; Parkinson Disease; Gait Disorders, Neurologic; Heart Rate; Gait; Movement; Tremor
PubMed: 37106388
DOI: 10.1186/s12984-023-01175-y -
Movement Disorders Clinical Practice Apr 2023On-demand treatments can treat OFF episodes in Parkinson's disease, however, there is limited information regarding when to prescribe them.
BACKGROUND
On-demand treatments can treat OFF episodes in Parkinson's disease, however, there is limited information regarding when to prescribe them.
OBJECTIVE
Develop expert consensus to determine appropriate clinical factors for considering on-demand treatments.
METHODS
Using a RAND/UCLA modified Delphi panel method, a panel developed consensus on the use of on-demand treatments for OFF episodes.
RESULTS
The panel agreed on-demand treatments were appropriate when OFF episodes were associated with greater functional impact and interfered with basic daily activities. The panel also agreed on-demand treatment may be appropriate for patients with morning akinesia and/or delayed ON of first levodopa dose and >1 type of OFF episode (eg, early morning OFF or wearing OFF regardless of frequency).
CONCLUSIONS
Experts agreed on-demand treatment is appropriate for many patients with OFF episodes. The greater the functional impact of OFF episodes, the more likely experts agreed that on-demand treatment is appropriate to prescribe.
PubMed: 37070052
DOI: 10.1002/mdc3.13690 -
Cureus Mar 2023Although Takotsubo syndrome (TS) has been long recognized, it is now more frequently identified as a cause of stress-induced cardiac injury since its first description...
Although Takotsubo syndrome (TS) has been long recognized, it is now more frequently identified as a cause of stress-induced cardiac injury since its first description in the 1990s. While most cases are transient, many patients can have acute and long-term effects including persistent or worsening heart failure, arrhythmia, cardiac thrombi, outflow tract obstruction, ventricular wall rupture, and cardiogenic shock. Medical optimization is necessary to prevent cardiac remodeling and disease recurrence and manage associated heart failure. The choice of medications may vary from patient to patient based on the inciting factor or the most probable cause. Anticoagulation can be added for a small period of time if there is a concern for thrombus formation from akinesia/dyskinesia. Most patients achieve early recovery and resolution of symptoms and those with persistent manifestations can be managed medically.
PubMed: 37056535
DOI: 10.7759/cureus.36056 -
Experimental Brain Research May 2023Neural processing in the basal ganglia is critical for normal movement. Diseases of the basal ganglia, such as Parkinson's disease, produce a variety of movement...
Neural processing in the basal ganglia is critical for normal movement. Diseases of the basal ganglia, such as Parkinson's disease, produce a variety of movement disorders including akinesia and bradykinesia. Many believe that the basal ganglia influence movement via thalamic projections to motor areas of the cerebral cortex and through projections to the cerebellum, which also projects to the motor cortex via the thalamus. However, lesions that interrupt these thalamic pathways to the cortex have little effect on many movements, including limb movements. Yet, limb movements are severely impaired by basal ganglia disease or damage to the cerebellum. We can explain this impairment as well as the mild effects of thalamic lesions if basal ganglia and cerebellar output reach brainstem motor regions without passing through the thalamus. In this report, we describe several brainstem pathways that connect basal ganglia output to the cerebellum via nucleus reticularis tegmenti pontis (NRTP). Additionally, we propose that widespread afferent and efferent connections of NRTP with the cerebellum could integrate processing across cerebellar regions. The basal ganglia could then alter movements via descending projections of the cerebellum. Pathways through NRTP are important for the control of normal movement and may underlie deficits associated with basal ganglia disease.
Topics: Humans; Cerebellum; Basal Ganglia; Movement; Neural Pathways
PubMed: 37000205
DOI: 10.1007/s00221-023-06574-0 -
Journal of Medical Genetics Sep 2023Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they...
BACKGROUND
Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they cause a wide spectrum of recessive phenotypes with a congenital or childhood onset. Most recessive phenotypes showing a congenital or childhood onset have been described in subjects carrying biallelic TTNtv in specific exons. Often karyotype or chromosomal microarray analyses are the only tests performed when prenatal anomalies are identified. Thereby, many cases caused by defects might be missed in the diagnostic evaluations. In this study, we aimed to dissect the most severe end of the titinopathies spectrum.
METHODS
We performed a retrospective study analysing an international cohort of 93 published and 10 unpublished cases carrying biallelic TTNtv.
RESULTS
We identified recurrent clinical features showing a significant correlation with the genotype, including fetal akinesia (up to 62%), arthrogryposis (up to 85%), facial dysmorphisms (up to 73%), joint (up to 17%), bone (up to 22%) and heart anomalies (up to 27%) resembling complex, syndromic phenotypes.
CONCLUSION
We suggest to be carefully evaluated in any diagnostic process involving patients with these prenatal signs. This step will be essential to improve diagnostic performance, expand our knowledge and optimise prenatal genetic counselling.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Connectin; Retrospective Studies; Muscle, Skeletal; Myocardium
PubMed: 36977548
DOI: 10.1136/jmg-2022-109018 -
Frontiers in Neurology 2023Sleep disturbances and excessive daytime sleepiness (EDS) are common non-motor symptoms in patients with Parkinson's disease (PD). The purpose of this study was to...
BACKGROUND
Sleep disturbances and excessive daytime sleepiness (EDS) are common non-motor symptoms in patients with Parkinson's disease (PD). The purpose of this study was to identify the contributors to sleep disturbances, including insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder (RBD), sleep-disordered breathing, nocturnal akinesia and EDS, in patients with PD.
METHODS
We conducted a cross-sectional study including 128 consecutive Japanese patients with PD. Sleep disturbances and EDS were defined as a PD Sleep Scale-2 (PDSS-2) total score ≥15 and an Epworth Sleepiness Scale (ESS) score >10, respectively. The patients were divided into four groups according to the presence or absence of sleep disturbances and EDS. We evaluated the disease severity, motor symptoms, cognition, olfactory test, the Scales for Outcomes in PD-Autonomic dysfunction (SCOPA-AUT), the Beck Depression Inventory-II (BDI-II), and the RBD Screening Questionnaire Japanese version (RBDSQ-J).
RESULTS
Of 128 patients, 64 had neither EDS nor sleep disturbances, 29 had sleep disturbances without EDS, 14 had EDS without sleep disturbances, and 21 had both EDS and sleep disturbances. Patients with sleep disturbances had higher BDI-II scores than those without sleep disturbances. Probable RBD was more frequent in patients with both sleep disturbances and EDS than in those with neither EDS nor sleep disturbances. The SCOPA-AUT score was lower in patients with neither EDS nor sleep disturbances than in patients in the other three groups. Using multivariable logistic regression analysis with neither sleep disturbances nor EDS as a reference group, that the SCOPA-AUT score was an independent contributor to sleep disturbances (adjusted OR, 1.192; 95% CI, 1.065-1.333; = 0.002) or EDS (OR, 1.245; 95% CI, 1.087-1.424; = 0.001) and that the BDI-II (OR, 1.121; 95% CI, 1.021-1.230; = 0.016) and RBDSQ-J scores (OR, 1.235; 95% CI, 1.007-1.516; = 0.043) as well as the SCOPA-AUT score (OR, 1.137; 95% CI, 1.006-1.285; = 0.040) were independent contributors to both sleep disturbances and EDS.
CONCLUSIONS
Autonomic symptoms were associated with patients with sleep disturbances or EDS, and depressive and RBD symptoms in addition to autonomic symptoms were associated with patients with both sleep disturbances and EDS.
PubMed: 36970510
DOI: 10.3389/fneur.2023.1097251 -
Indian Journal of Pharmacology 2023Subtenon's block is commonly used to achieve akinesia, analgesia, and anesthesia for ophthalmic surgeries. This case study detailed a rare hypersensitivity report in a...
Subtenon's block is commonly used to achieve akinesia, analgesia, and anesthesia for ophthalmic surgeries. This case study detailed a rare hypersensitivity report in a 65-year-old female who had underwent manual small incision cataract surgery under subtenon's anesthesia (STA) in the left eye. On postoperative day 1, she presented with acute onset proptosis, periorbital edema, conjunctival chemosis, and restriction of extraocular movements. The pupillary reaction and dilated fundus examination were normal. A differential diagnosis of orbital cellulitis, Mucormycosis, and hyaluronidase hypersensitivity (HH) was considered. Since the patient was afebrile, and pupillary reactions, ENT, neurological, and fundus examination were normal, the diagnosis was narrowed down to delayed HH. The patient was managed with a 1 cc IV injection of dexamethasone once a day for 3 days, along with routine postoperative drugs. As per detailed literature review, this is probably a second case report of delayed HH post-STA.
Topics: Female; Humans; Aged; Hyaluronoglucosaminidase; Pandemics; COVID-19; Anesthesia, Local
PubMed: 36960522
DOI: 10.4103/ijp.ijp_995_21