Lesions Of Neurons Research Articles

Impact of Combined Neuromuscular Electrical Stimulation (Comb-NMES) on Glucose Signaling and Muscle Myofiber Distribution in a Patient with Acute Spinal Cord Injury and Lower Motor Neuron Lesion

Introduction: This case report examines the impact of a novel combined neuromuscular electrical stimulation (Comb-NMES) regimen on muscle glucose signaling, fiber type distribution, and metabolic function in a patient with acute spinal cord injury (SCI) and lower motor neuron lesions (LMNLs). Case Report: A 32-year-old male with complete T9 SCI underwent a ten-session Comb-NMES intervention targeting the quadriceps. Muscle biopsies and blood samples were analyzed pre- and post-intervention to evaluate changes in muscle fiber types, key metabolic proteins, fasting insulin, glucose, and lipid profiles. Results: The intervention led to a 74.7% and 28.2% reduction in fasting insulin and glucose, respectively. Muscle analysis showed significant increases in CaMK II, Hexokinase II, and IRS-1, indicating improved glucose metabolism. Conclusion: Comb-NMES training markedly improved metabolic control and muscle glucose metabolism in a patient with acute SCI and LMNLs. Enhanced insulin sensitivity and glucose utilization were evidenced by upregulated metabolic proteins, which suggests that Comb-NMES is a promising intervention for improving muscle and metabolic health in SCI patients with LMNLs. Further studies are needed to confirm these benefits and explore the long-term effects.

Analysis of Upper Facial Weakness in Central Facial Palsy Following Acute Ischemic Stroke.

Central facial palsy (CFP), resulting from upper motor neuron lesions in the corticofacial pathway, is traditionally characterized by the sparing of the upper facial muscles. However, reports of upper facial weakness in CFP due to acute ischemic stroke have challenged this long-held assumption. This study aimed to determine the prevalence of upper facial weakness in CFP and identify its associated clinical factors. In this cross-sectional study, we evaluated consecutive patients with acute ischemic stroke admitted to a university hospital in Thailand from January 2022 to June 2023. Full-face video recordings were analyzed using the Sunnybrook Facial Grading System. Upper facial weakness was defined as asymmetry in at least one upper facial expression. Multivariable logistic regression was performed to identify factors associated with upper facial weakness. Of 108 patients with acute ischemic stroke, 92 had CFP, and among these, 70 (76%) demonstrated upper facial weakness. Tight eye closure (force and wrinkle formation, both 42%) was the most sensitive indicator for detecting upper facial weakness. Greater stroke severity, as reflected by higher NIHSS scores (adjusted odds ratio [aOR], 1.42; 95% CI 1.07-1.88) and the presence of lower facial weakness (aOR, 6.56; 95% CI 1.85-23.29) were significantly associated with upper facial involvement. Although upper facial weakness was generally milder than lower facial weakness, its severity correlated with increasing lower facial asymmetry during movement. Contrary to traditional teaching, upper facial weakness is common in CFP due to acute ischemic stroke. The severity of stroke and the presence of lower facial weakness are key predictors of upper facial involvement. These findings underscore the need for clinicians to reconsider the diagnostic paradigm, recognizing that upper facial weakness can occur in CFP. Enhanced awareness may improve diagnostic accuracy, inform treatment decisions, and ultimately lead to better patient outcomes.

Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson’s disease model triggered by α-synuclein overexpression

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson’s disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia. This chronic treatment paradigm prevented the development of motor deficits and concomitantly preserved dopaminergic neuron cell and weakened α-synuclein phosphorylation. Gene expression profiles related to extracellular matrix (ECM) remodeling were increased after microglia depletion in PD mice, which were further validated on protein level. We demonstrated that microglia exert adverse effects during α-synuclein-overexpression-induced neuronal lesion formation, and their depletion remodels ECM and aids recovery following insult.

Hereditary spastic paraplegias: When to expect bladder dysfunction a genetic and urodynamic study.

The aim of this study was to characterize hereditary spastic paraplegias (HSP) patients' urodynamic profiles and development of bladder symptoms. This is a multicentric retrospective study which included patients presenting with bladder disorders. We reviewed medical and urodynamic records in individuals with HSP and recorded age at onset of gait and bladder disorders, disability stage at the time of urodynamic assessment. We included 122 participants. They were mostly men (n = 74) with a median age at interview of 54.6 ± 13.0 [25-76] years. The underlying genetic cause was identified in 70% of participants, with 54 heterozygous mutations in SPAST, followed by 7 SPG11 and 6 SPG7. The age at onset of motor disorder was significantly younger than for the beginning of bladder dysfunction (49.3 vs. 29.7 years-old, p < 0.001). Detrusor overactivity was present in most participants (72.1%), followed by detrusor-sphincter-dyssynergia (65.3%). Similar proportions were present in the SPAST group as well as the non-SPAST group. The SPAST group developed urinary symptoms later than the non-SPAST group as compared to the age at onset of spasticity (53.8 ± 11.3 and 44.1 ± 13.2 for the SPAST group vs. 44.1 ± 13.2 and 25.5 ± 17.3 for the non-SPAST group). We have shown that the most common urodynamic pattern in HSP is detrusor overactivity associated with detrusor-sphincter dyssynergia, as would be expected for upper motor neuron lesions. We assessed the temporal window of onset, showing that urinary disorders are secondary to spastic gait in HSP and particularly frequent when walking capability deteriorates.

Canonical MAPK signaling in auditory neuropathy.

Auditory neuropathy (AN) is an under-recognized form of hearing loss characterized by lesions in inner hair cells (IHCs), ribbon synapses and spiral ganglion neurons (SGNs). The lack of a targeted therapy for AN has increased the need for a better understanding of the pathogenic mechanism of AN. As mitogen-activated protein kinase (MAPK) signaling is ubiquitous in many biological processes, its alteration may facilitate the pathogenesis of multiple sites in AN. Here, we summaries the characteristics of AN under different molecular bases and first explore the mechanism of MAPK at different lesion sites. Alterations of extracellular signal-regulated kinase (ERK)/MAPK occur in IHCs and SGNs, whereas modulations of p38 and c-Jun NH2-terminal kinase (JNK) were found in ribbon synapses and SGNs. In conclusion, inductive MAPK alterations in the pathogenesis and development of AN are likely to represent a potential therapeutic target to guide the development of treatments.

Impaired Basal Forebrain Cholinergic Neuron GDNF Signaling Contributes to Perioperative Sleep Deprivation-Induced Chronicity of Postsurgical Pain in Mice Through Regulating Cholinergic Neuronal Activity, Apoptosis, and Autophagy.

This study investigated the roles of lateral basal forebrain glial cell line-derived neurotrophic factor (GDNF) signaling and cholinergic neuron activity, apoptosis, and autophagy dysfunction in sleep deprivation-induced increased risk of chronic postsurgical pain (CPSP) in mice. Sleep deprivation (6 h per day from -1 to 3 days postoperatively) was administered to mice receiving skin/muscle incision and retraction (SMIR) to determine whether perioperative sleep deprivation induces mechanical and thermal pain hypersensitivity, increases the risk of chronic pain, and causes changes of basal forebrain neurons activity (c-Fos immunostaining), apoptosis (cleaved Caspase-3 expression), autophagy (LC3 and p62 expression) and GDNF expression. Adeno-associated virus (AAV)-GDNF was microinjected into the basal forebrain to see whether increased GDNF expression could reverse sleep deprivation-induced changes in pain duration and cholinergic neuron apoptosis and autophagy. Cholinergic neurons were further depleted by mu p75-SAP to examine whether the pain-prolonging effects of sleep deprivation still exist. Perioperative sleep deprivation enhanced pain sensation and prolonged pain duration in SMIR mice, which was accompanied by decreased cholinergic neuron activity and GDNF expression, increased apoptosis, and autophagy dysfunction in the substantia innominata (SI), magnocellular preoptic nucleus (MCPO), and horizontal diagonal band Broca (HDB) (hereafter lateral basal forebrain). Normalizing cholinergic neuron GDNF expression by AAV-GDNF in the lateral basal forebrain inhibited apoptosis and autophagy dysfunction and mitigated sleep deprivation-induced pain maintenance. Mice with selective lesion of lateral basal forebrain cholinergic neurons were resistant to the pain-enhancing and prolonging effects of sleep deprivation and the pain-alleviating effects of AAV-GDNF therapy. Perioperative sleep deprivation promotes chronicity of postsurgical pain possibly through decreasing basal forebrain GDNF signaling and causing cholinergic neuronal apoptosis and autophagy dysfunction.

Isolated expressive aphasia caused by acute subdural hematoma: case report and literature review

The occurrence of aphasia as an isolated and dominant clinical feature of acute subdural hematoma (aSDH) has been rarely mentioned in the available literature. Being the most common focal intracranial lesion, subdural hematomas (SDH) pose a clinical challenge, especially when presented with unorthodox clinical features. We report a case of a patient with a traumatic aSDH, presenting with intense frontal headaches and normal neurological examination. On the 3rd postadmission day, he developed expressive dysphasia which progressed to aphasia, with neurological examination findings of an upper motor neuron lesion (UMNL), without hematoma expansion, verified via head CT (computed tomography). The patient underwent decompressive craniotomy and hematoma evacuation. Early speech improvements were noted immediately postoperatively, and at hospital discharge the patient had no evident clinical features of speech disorder and neurological deficits or tests suggesting UMNL. Speech disorders in the setting of an aSDH need to be further investigated and potentially considered as an indication for surgical management, especially in rare instances where they present as an isolated clinical feature and conservative treatment is initially considered.

SEP-363856 attenuates CUMS-induced depression-like behaviours and reverses hippocampal neuronal injuries

Objectives This study employed a chronic unpredictable mild stress (CUMS) model to examine the antidepressant properties of SEP-363856. Methods The sucrose preference test (SPT) was employed to evaluate anhedonia, the open field test (OFT) to measure locomotor activity and exploratory behaviour, the elevated plus-maze (EPM) to assess anxiety-like behaviour, and the tail suspension test (TST) and forced swimming test (FST) to determine despair behaviour. qRT-PCR was implemented to evaluate gene expression levels in the hippocampus. Western blot, and ELISA were implemented to evaluate hippocampal protein expression, and Nissl staining was implemented to identify hippocampal neuronal injury. Results The 10 mg/kg dosage of SEP-363856 and fluoxetine significantly improved depressive-like behaviours as assessed by the SPT, OFT, EPM, TST, and FST. This was associated with improved hippocampal neuronal damage, enhanced mRNA expression of brain-derived neurotrophic factor, synaptophysin, and postsynaptic density 95. SEP-363856 increased the levels of insulin-like growth factor-1 (IGF-1), IGF-1 receptor β, phospho-phosphatidylinositide 3-kinase, and phospho-protein kinase B in the brain. Conclusions The antidepressant-like effects of SEP-363856 are linked to increased hippocampal neurotrophic factors, decreased hippocampus neuronal lesions, and activation of the IGF-1Rβ/PI3K/AKT signalling pathway. The latter may serve as a novel drug target for the treatment of depression.

Patient Reported Outcomes Due to Bladder Neck Obstruction in Women Treated With Botulinum Toxin A Injection.

Primary bladder neck obstruction (BNO) occurs when the bladder neck fails to open during voiding, causing urinary symptoms despite no anatomic obstruction. The cause of BNO is unclear but may involve neurogenic dysregulation related to the sympathic nervous system such as upper motor neuron lesion or peripheral autonomic neuropathy (small fiber neuropathy (SFN)). Another etiology can incuded increased sympathetic tone secondary to anxiety or stress conditons. Botulinum toxin A (BoNT-A) to the bladder neck has been used in our practice to treat women with BNO who failed conventional therapies (alpha blockers, relaxation strategies). This is the first report of patient-reported outcomes after BoNT-A treatment in women with pelvic pain and BNO. We included female patients with pelvic pain and BNO who received BoNT-A to the bladder neck between January 2022 and March 2023, and mailed self-reported outcome questionnaires. The primary outcome was the Global Response Assessment (GRA); secondary outcomes included pain scores on the Visual Analogue Scale (VAS) and symptom checklists. BNO was diagnosed using Nitti Criteria (high bladder pressure, low flow in bladder neck on video urodynamics), supplemented by additional criteria (e.g., high voiding pressure, prolonged attempts, Valsalva effort, and cystoscopic evidence or symptoms related to BNO). Urodynamic studies followed International Continence Society standards. Additionally, due to BNO's association with SFN, patient history of biopsy-confirmed SFN was recorded. Our inclusion criteria was satisfied among 18 patietns, with 17 completing the questionnaire. Out of those, 14 patients (77%) reported improvement on the GRA, with an average VAS of 8.3 ("Very Helpful"). The most commonly improved symptoms were feeling of incomplete emptying, difficulty starting stream, urethral burning, pain with urination, and pelvic pain. Postoperative symptom flares were reported in six patients for an average of 16 days. All six patients with biopsy-confirmed SFN showed significant improvement (VAS 8.7). Total of 14 patients (77%) indicated they would repeat the procedure. BoNT-A to the bladder neck significantly improved pelvic pain and refractory hesitancy in women with bladder neck obstruction, especially in those with small fiber neuropathy. Symptom flares are common, but did not reduce interest in repeated treatments, and scheduling injections before symptom recurrence may mitigate these flares.

Effectiveness of Game-Based Training of Selective Voluntary Motor Control in Children With Upper Motor Neuron Lesions: Randomized Multiple Baseline Design Study.

Selective voluntary motor control (SVMC) is the ability to control joint movements independently. Impairments in SVMC can affect functional activities, but only a few interventions directly target SVMC. Therefore, we developed a game-based intervention for children with upper motor neuron lesions to improve SVMC. The intervention trained selective activation of a muscle or joint movement while providing immediate feedback about involuntarily occurring muscle activations or movements in another joint. The intervention was provided in a playful manner with a custom-made game environment and a technology-based interface to capture muscle activation or joint movements. This study aimed to investigate the effectiveness of this game-based intervention and explore treatment response-related factors in children with impaired SVMC undergoing inpatient neurorehabilitation. We conducted a single-case research study with a randomized, nonconcurrent, multiple baseline design. The study consisted of a random-length baseline phase where no SVMC-specific intervention was provided and an intervention phase with additional SVMC training. Concurrently in both phases, children attended their individual multimodal rehabilitation program at our clinic, Swiss Children's Rehab. During the intervention phase, participants completed ten 45-minute sessions with our game-based SVMC training. SVMC was measured repeatedly throughout both phases and at the 3-month follow-up with a short custom-made assessment. Eighteen children with reduced SVMC from upper motor neuron lesions participated in the study. The mean age of the children was 12.7 (SD 2.9) years, and they mostly had spastic cerebral palsy. A linear mixed-effects model revealed a significant trend (P<.001) for improved SVMC already in the baseline phase. This trend did not change significantly (P=.15) when the game-based SVMC training was introduced in the intervention phase, suggesting no additional improvements due to the SVMC training. Although we could not find an overall treatment effect, we could explain 89.4% of the total random variation of the treatment effect by patient and therapy characteristics. Children with spasticity in the trained movement (20.1%), and those who trained the more affected side (23.5%) benefited most from the intervention. At the 3-month follow-up, SVMC had deteriorated compared to the end of the intervention but was still better than at the beginning of the study. The regular concomitant rehabilitation program already yielded improvements in SVMC, while the game-based SVMC training showed no additional effects. Although the intervention did not show a group effect, we could identify patient and therapy characteristics that determine who is likely to profit from the intervention. German Clinical Trials Register DRKS00025184; https://tinyurl.com/msnkek9b.

Multinodular Vacuolating Neuronal Tumors: Symptomatic Presentation Versus Incidental Finding: Case Series and Literature Review

Background: Multinodular Vacuolating Neuronal Tumors (MVNTs) are mixed glial–neuronal brain lesions classified as World Health Organization (WHO) CNS grade 1 tumors, often associated with long-term epilepsy. First described by Huse et al. in 2013 and included in the WHO CNS classification in 2016, MVNTs present a range of clinical manifestations, from symptomatic to asymptomatic. They typically affect young to middle-aged adults and exhibit diverse presentations. Radiologically, MVNTs are usually supratentorial, frequently located in the temporal lobe but also observed in the frontal and parietal lobes. MRI is essential for diagnosis, revealing multiple coalescing subcortical or cortical nodules with hyperintense signals on T2-weighted/FLAIR sequences, often without peripheral edema or mass effects. Case Reports: This paper presents two cases: one symptomatic MVNT with significant clinical manifestations, and the other documenting an incidental finding of MVNT in an asymptomatic patient. One case shows typical temporal lobe localization, while the other highlights a rare frontal lobe localization, with clear radiological findings on T2/FLAIR sequences. Conclusions: These cases illustrate the varied clinical presentations of MVNTs and emphasize MRI’s critical role in diagnosis and management. Asymptomatic cases often require conservative management, stressing the avoidance of unnecessary invasive procedures and the importance of regular monitoring.

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis

AimSepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms. MethodsPatients with sepsis and healthy controls were included. Sepsis in rats was induced by lipopolysaccharide. Dexmedetomidine, a α2-adrenergic receptor agonist, was used in patients and rats with sepsis to evaluate the role of the sympathetic nervous system in sepsis. Holter monitoring was used to detect heart rate variability, while plasma samples were obtained to measure levels of norepinephrine and inflammatory markers. Mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded. Immunofluorescence was used to detect the activation of neurons in the rostral ventrolateral medulla (RVLM). ResultsIn patients with sepsis, plasma levels of norepinephrine and interleukin-1β were higher compared with those in controls and positively correlated with acute physiology and chronic health evaluation (APACHE) II. SDNN and SDANN were significantly reduced as well as negatively correlated with APACHE II. Meanwhile, rats with sepsis showed increased of sympathetic outflow and plasma levels of norepinephrine, with increased c-fos levels in the RVLM. Treatment with dexmedetomidine could improve prognosis. Lesion of tyrosine hydroxylase-positive neurons in the RVLM attenuated sympathetic activation and target organs damage in septic rats as well as improved survival. ConclusionThe results suggest that tyrosine hydroxylase-positive neurons in the RVLM might contribute to the prognosis of sepsis via activation of the sympathetic nervous system, while dexmedetomidine could ameliorate sepsis via inhibiting sympathetic activation.

Effects of dopaminergic neuron degeneration on osteocyte apoptosis and osteogenic markers in 6-OHDA male rat model of Parkinson's disease

Parkinson's disease (PD) and osteoporosis are prevalent chronic conditions that impact a significant proportion of the aging population. Observational and longitudinal studies consistently demonstrate that individuals with PD face an elevated risk of osteoporosis and reduced bone mineral density compared to control groups. However, there is currently no experimental evidence demonstrating the impact of dopaminergic neuron degeneration on bone metabolism. In the present study, we used a male rat model of PD induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the left medial forebrain bundle (MFB) to evaluate the effect of dopaminergic neuron lesion on certain parameters of bone metabolism. To confirm the dopaminergic neuron lesion, cylinder and Rotarod tests were applied to rats injected with 6-OHDA or vehicle. Osteocyte density and viability were determined through histology and TUNEL assay. Western Blot and immunohistochemistry analysis were performed to investigate whether dopaminergic degeneration influences the expression of some apoptotic markers (Caspase 3 and Cytochrome C) and some osteogenic markers (ALP, OCN, and RUNX2). Our findings show that the dopaminergic lesion resulting from the injection of 6-OHDA was successfully confirmed through behavioral tests. Furthermore, the degeneration of dopaminergic neurons induced by 6-OHDA leads to apoptosis of osteocytes associated with a significant reduction in the tissue expression of the studied osteogenic markers. Thus, our study provides evidence that 6-OHDA-induced degeneration of dopaminergic neurons leads to osteocyte apoptosis, which may contribute to the development of some signs of osteoporosis.

Dyke-Davidoff-Masson Syndrome in a Tanzanian patient: a case report

BackgroundDyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological disorder resulting from an insult to the developing brain in utero or during early life which is characterized by refractory seizures and a wide variety of deficits. Due to its rarity, the condition is often overlooked although a detailed history and imaging can help distinguish it from other similar conditions and provide early diagnosis.Case presentationA 30-year-old African female presented with a history of recurrent seizures and intellectual disability. She was born via vaginal delivery, and her post-natal history was unremarkable. Her developmental milestones were normal until the age of three, when she was hospitalized for two weeks due to a febrile illness accompanied by generalized seizures, from which she fully recovered. On cognitive assessment, she scored 14 out of 60 on the Ravens Standard Progressive Matrices (RSPM), indicating an intellectual disability. Neurological examination revealed constructional apraxia, an upper motor neuron lesion (UMNL) affecting the facial nerve, and left-sided spastic paresis. Additionally, a slow, sinuous writhing movement involving all the fingers of her left hand was observed. A computed tomography (CT) scan of her head confirmed a diagnosis of Dyke-Davidoff-Masson syndrome (DDMS). The scan showed significant volume loss in the right cerebral hemisphere, gross dilation of the right lateral ventricle with ex-vacuo dilatation, right calvarial thickening, and hyperpneumatization of the right frontal sinus. She was managed conservatively with anticonvulsants, which effectively controlled her seizures.ConclusionIn the setting of recurrent seizures, intellectual disability, hemiparesis, or facial asymmetry, a clinician should have a high index of suspicion for DDMS. Late diagnosis is often related to intractable seizures to anticonvulsants, necessitating hemispherectomy, which is not a readily available option in limited resource settings.

Role of the Nucleus Accumbens in Signaled Avoidance Actions.

Animals, humans included, navigate their environments guided by sensory cues, responding adaptively to potential dangers and rewards. Avoidance behaviors serve as adaptive strategies in the face of signaled threats, but the neural mechanisms orchestrating these behaviors remain elusive. Current circuit models of avoidance behaviors indicate that the nucleus accumbens (NAc) in the ventral striatum plays a key role in signaled avoidance behaviors, but the nature of this engagement is unclear. Evolving perspectives propose the NAc as a pivotal hub for action selection, integrating cognitive and affective information to heighten the efficiency of both appetitive and aversive motivated behaviors. To unravel the engagement of the NAc during active and passive avoidance, we used calcium imaging fiber photometry to examine NAc GABAergic neuron activity in ad libitum moving mice performing avoidance behaviors. We then probed the functional significance of NAc neurons using optogenetics and genetically targeted or electrolytic lesions. We found that NAc neurons code contraversive orienting movements and avoidance actions. However, direct optogenetic inhibition or lesions of NAc neurons did not impair active or passive avoidance behaviors, challenging the notion of their purported pivotal role in adaptive avoidance. The findings emphasize that while the NAc encodes avoidance movements, it is not required for avoidance behaviors, highlighting the distinction between behavior encoding or representation and mediation or generation.

The Tree Shrew Model of Parkinson Disease: A Cost-Effective Alternative to Nonhuman Primate Models

The surge in demand for experimental monkeys has led to a rapid increase in their costs. Consequently, there is a growing need for a cost-effective model of Parkinson disease (PD) that exhibits all core clinical and pathologic phenotypes. Evolutionarily, tree shrews (Tupaia belangeri) are closer to primates in comparison with rodents and could be an ideal species for modeling PD. To develop a tree shrew PD model, we used the 1-methyl-4-phenylpyridinium (MPP+), a metabolite derived from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to induce lesions in dopaminergic neurons of the unilateral substantia nigra. The induced tree shrew model consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms included bradykinesia, rest tremor, and postural instability, and ∼50% individuals showed apomorphine-induced rotations, a classic phenotype of unilateral PD models. All these are closely resembled the ones observed in PD monkeys. Meanwhile, this model was also sensitive to L-dopa treatment in a dose-dependent manner, which suggested that the motor deficits are dopamine dependent. Immunostaining showed a significant loss of dopaminergic neurons (∼95%) in the lesioned substantia nigra, which is a crucial PD pathological marker. Moreover, a control group of nigral saline injection did not show any motor deficits and pathological changes. Cytomorphologic analysis revealed that the size of nigral dopaminergic neurons in tree shrews is much bigger than that of rodents and is close to that of macaques. The morphologic similarity may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, in this study, we have successfully developed a PD model in a small animal species that faithfully recapitulated the classic clinical symptoms and key pathological indicators of PD monkeys, providing a novel and low-cost avenue for evaluation of PD treatments and underlying mechanisms.

Ultrastructural Analysis of the Large Neuronal Perikarya in an Injured Dentate Nucleus Using an Experimental Model of Hyperthermia-Induced Convulsions: The First Qualitative and Quantitative Study.

Background: Febrile seizures are a common form of convulsions in childhood, with poorly known cellular mechanisms. The objective of this pioneering study was to provide qualitative and quantitative ultrastructural research on the large neuronal perikarya in the cerebellar dentate nucleus (DN), using an experimental model of hyperthermia-induced seizures (HSs), comparable to febrile seizures in children. Methods: The study used young male Wistar rats, divided into experimental and control groups. The HSs were evoked by a hyperthermic water bath at 45 °C for 4 min for four consecutive days. Specimens (1 mm3) collected from the DN were routinely processed for transmission electron microscopy studies. Results: The ultrastructure of the large neurons in the DN affected by hyperthermic stress showed variously pronounced lesions in the perikarya, including total cell disintegration. The most pronounced neuronal lesions exhibited specific morphological signs of aponecrosis, i.e., dark cell degeneration ('dark neurons'). In close vicinity to the 'dark neurons', the aponecrotic bodies were found. The findings of this qualitative ultrastructural study correspond with the results of the morphometric analysis of the neuronal perikarya. Conclusions: Our results may constitute interesting comparative material for similar submicroscopic observations on large DN neurons in HS morphogenesis and, in the future, may help to find potential treatment targets to prevent febrile seizures or reduce recurrent seizures in children.

Brachialis to Anterior Interosseous Nerve Transfer: Comprehensive Anatomic Rationale.

Distal nerve transfers for muscle reinnervation and restoration of function after upper and lower motor neuron lesions are a well-established surgical approach. The brachialis to anterior interosseous nerve (BrAIN) transfer is performed for prehension reanimation in lower brachial plexus and traumatic cervical spinal cord injuries. The aim of the study is to shed light on the inconsistent results observed in patients who undergo the BrAIN transfer. An anatomic dissection was conducted on 30 fresh upper limb specimens to examine the intraneural topography of the median nerve (MN) in the upper arm at the level of the BrAIN transfer and the presence of intraneural fascicular interconnections distally. Fascicular interconnections between the AIN and other MN branches were consistently found in the distal third of the upper arm. The first interconnection was at 3.85 ± 1.82 cm proximal to the interepicondylar line, and the second one, after further proximal neurolysis, was at 9.45 ± 1.16 cm from the interepicondylar line. Intraneural topography of the AIN at the transfer level varied, with dorsomedial, dorsolateral, and purely dorsal locations observed. Consistent fascicular interconnections between the AIN and MN branches and intraneural topography variability of the MN may lead to aberrant reinnervation.

Blood-brain barrier breach after acute cerebral hypoxia in infants

Background. Neuronal lesion, including hypoxic-ischemic damage to the central nervous system (CNS) in perinatal period, leads to the release of neuron-specific enolase (NSE) into peripheral bloodstream. Consequently, NSE can be considered as a biological marker of nervous system injury. Based on NSE level analysis, timely rehabilitation for newborns can be provided, thereby reducing the likelihood of complications associated with CNS injury.Objective: retrospective assessment of NSE level in peripheral blood over a 24-week period in infants of different gestational age with perinatal hypoxic-ischemic CNS damage.Material and methods. The study included 49 newborns who had suffered perinatal hypoxic-ischemic CNS lesion. Gestation period differed from 32 to 41 weeks. The control group consisted of 28 healthy full-term infants. NSE levels were measured using enzyme immunoassay. Patients of the main group were additionally divided into subgroups depending on Apgar scores at the 1st minute after birth, gestational age, as well as predominant CNS lesion – hemorrhagic with intraventricular hemorrhages or ischemic with periventricular leukomalacia.Results. Throughout the observation period, NSE concentrations were inversely correlated with Apgar scores: lower Apgar indicators were associated with higher NSE levels. In addition, the subgroup of 32–33-week gestational age had significantly higher NSE concentrations compared with 34–36-week, 37–41-week subgroups, and control group. NSE levels in infants with periventricular leukomalacia were consistently lower than those in newbornes with intraventricular hemorrhage starting from the 1st week. Notably, a delayed increase in serum NSE concentrations was observed at the 4th week.Conclusion. The obtained data indicate that blood-brain barrier permeability for NSE is preserved during perinatal hypoxicischemic CNS injury. Serum NSE concentration measurement can serve as a valuable tool in clinical practice for assessing the effectiveness of therapy at the stages of treatment and rehabilitation.

Experimental Periodontitis Worsens Dopaminergic Neuronal Degeneration.

To investigate the hypothesis supporting the link between periodontitis and dopaminergic neuron degeneration. Adult male Wistar rats were used to induce dopaminergic neuronal injury with 6-hydroxydopamine (6-OHDA) neurotoxin and experimental periodontitis via ligature placement. Motor function assessments were conducted before and after periodontitis induction in controls and 6-OHDA-injury-induced rats. Tissue samples from the striatum, jaw and blood were collected for molecular analyses, encompassing immunohistochemistry of tyrosine hydroxylase, microglia and astrocyte, as well as micro-computed tomography, to assess alveolar bone loss and for the analysis of striatal oxidative stress and plasma inflammatory markers. The results indicated motor impairment in 6-OHDA-injury-induced rats exacerbated by periodontitis, worsening dopaminergic striatal degeneration. Periodontitis alone or in combination with 6-OHDA-induced lesion was able to increase striatal microglia, while astrocytes were increased by the combination only. Periodontitis increased striatal reactive oxygen species levels and plasma tumour necrosis factor-alpha levels in rats with 6-OHDA-induced lesions and decreased the anti-inflammatory interleukin-10. This study provides original insights into the association between periodontitis and a neurodegenerative condition. The increased inflammatory pathway associated with both 6-OHDA-induced dopaminergic neuron lesion and periodontal inflammatory processes corroborates that the periodontitis-induced systemic inflammation may aggravate neuroinflammation in Parkinson's-like disease, potentially hastening disease progression.