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Cold Spring Harbor Perspectives in... Jul 2024The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms...
The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms and evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. Herein, we systematically review the literature over the past decade. Some models no longer serve the purpose of PD models. The primary objectives of this review are: First, to assist new investigators in navigating through available animal models and making appropriate selections based on the objective of the study. Emphasis will be placed on common toxin-induced murine models. And second, to provide an overview of basic technical requirements for assessing the nigrostriatal pathway's pathology, structure, and function.
PubMed: 38951030
DOI: 10.1101/cshperspect.a041643 -
European Journal of Pharmacology Jun 2024The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of...
Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.
The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.
PubMed: 38950834
DOI: 10.1016/j.ejphar.2024.176792 -
Aging Jun 2024As a common disease, cervical spondylosis (CS) results from the degeneration of the cervical intervertebral disc. However, there are still no effective clinical...
As a common disease, cervical spondylosis (CS) results from the degeneration of the cervical intervertebral disc. However, there are still no effective clinical strategies for the treatment of this disease. Needle-scalpel (Ns), a therapy guided by traditional Chinese medicine theory, alleviates intervertebral disc degradation and is widely used in the clinic to treat CS. Stromal cell-derived factor-1 (SDF-1) and its receptor CXC receptor 4 (CXCR4) in nucleus pulposus cells play an important role in CS onset and development. This study aimed to explore whether Ns can relieve pain and regulate the SDF-1/CXCR4 axis in nucleus pulposus cells to inhibit apoptosis, thereby delaying cervical intervertebral disc degradation in a rat model of CS. It was found that the Ns-treated groups exhibited higher mechanical allodynia scores than the model group, and H&E staining, MRI, and scanning electron microscopy revealed that Ns therapy inhibited intervertebral disc degeneration. Additionally, Ns therapy significantly inhibited increases in the RNA and protein expression levels of SDF-1 and CXCR4. Furthermore, these treatments alleviated the apoptosis of nucleus pulposus cells, which manifested as a decline in the proportion of apoptotic nucleus pulposus cells and inhibition of the decrease in the levels of Bcl-2/Bax. These findings indicated that Ns mitigated CS-induced pain, inhibited the apoptosis of nucleus pulposus cells, and alleviated intervertebral disc degeneration in CS rats. These effects may be mediated by specifically regulating the SDF-1/CXCR4 signaling axis. Based on these findings, we conclude that Ns might serve as a promising therapy for the treatment of CS.
PubMed: 38949514
DOI: 10.18632/aging.205959 -
Journal of Biomedical Materials... Jul 2024Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in...
Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.
PubMed: 38949056
DOI: 10.1002/jbm.a.37753 -
Indian Journal of Orthopaedics Jul 2024Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the... (Review)
Review
INTRODUCTION
Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the cartilage in the joints. Presently, there is no proven medical management to halt the progression of the disease in the early stages. The purpose of our systematic review is to analyze the possible metabolites and metabolic pathways that are specifically involved in OA pathogenesis and early treatment of the disease.
MATERIALS AND METHODS
The articles were collected from PubMed, Cochrane, Google Scholar, Embase, and Scopus databases. "Knee", "Osteoarthritis", "Proteomics", "Lipidomics", "Metabolomics", "Metabolic Methods", and metabolic* were employed for finding the articles. Only original articles with human or animal OA models with healthy controls were included.
RESULTS
From the initial screening, a total of 458 articles were identified from the 5 research databases. From these, 297 articles were selected in the end for screening, of which 53 papers were selected for full-text screening. Finally, 50 articles were taken for the review based on body fluid: 6 urine studies, 15 plasma studies, 16 synovial fluid studies, 11 serum studies, 4 joint tissue studies, and 1 fecal study. Many metabolites were found to be elevated in OA. Some of these metabolites can be used to stage the OA Three pathways that were found to be commonly involved are the TCA cycle, the glycolytic pathway, and the lipid metabolism.
CONCLUSION
All these studies showed a vast array of metabolites and metabolic pathways associated with OA. Metabolites like lysophospholipids, phospholipids, arginine, BCCA, and histidine were identified as potential biomarkers of OA but a definite association was not identified, Three pathways (glycolytic pathway, TCA cycle, and lipid metabolic pathways) have been found as highly significant in OA pathogenesis. These metabolic pathways could provide novel therapeutic targets for the prevention and progression of the disease.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43465-024-01169-5.
PubMed: 38948380
DOI: 10.1007/s43465-024-01169-5 -
Cureus May 2024Degenerative changes of the lumbar intervertebral disc are the most significant causes of enduring lower back pain. The possibility of the diagnosis is limited in people... (Review)
Review
Degenerative changes of the lumbar intervertebral disc are the most significant causes of enduring lower back pain. The possibility of the diagnosis is limited in people with this low back pain. Therefore, it is essential to identify the relevant back pain subgroups. The paraspinal muscles, that is, the muscles that attach to the spine, are necessary for the proper functioning of the spine and the body; insufficiency can result in back pain. Lower back pain disorders are strongly associated with altered function or structure of these paraspinal muscles, especially fibrosis and fatty infiltration. Modic changes are the bone marrow changes of the end plate in the vertebral body seen on MRI. These are strongly related to degeneration of the disc and are common in individuals with back pain symptoms. Articles were selected from Google Scholar using the terms 'Modic changes,' 'end plate changes,' 'paraspinal muscles,' and 'lower back pain. ' This article compiled different studies aiming to enhance the comprehension of biochemical processes resulting in the development of lumbar pain. Search using the keywords 'Modic changes,'' end plate changes lower back pain,' 'paraspinal muscles lower back pain,' and 'Modic changes lower back pain' on Google Scholar yielded 33000, 41000, 49400, and 17,800 results, and 958, 118, 890 and 560 results on Pubmed respectively.
PubMed: 38947594
DOI: 10.7759/cureus.61319 -
Journal of Veterinary Research Jun 2024Small ruminant lentiviruses (SRLV) cause multisystemic, degenerative and chronic disease in sheep and goats. There are five genotypes (A, B, C, D and E), of which A and...
INTRODUCTION
Small ruminant lentiviruses (SRLV) cause multisystemic, degenerative and chronic disease in sheep and goats. There are five genotypes (A, B, C, D and E), of which A and B are the most widespread. The purpose of this study was to evaluate the serotyping efficiency of the Eradikit SRLV Genotyping ELISA and the molecular typing efficiency of a newly developed nested real-time PCR targeting the long terminal repeat- (LTR-gag) region using samples from animals infected with subtypes of SRLV known to circulate in Poland.
MATERIAL AND METHODS
A total of 97 sera samples taken from 34 sheep and 63 goats were immunoassayed, and 86 DNA samples from 31 sheep and 55 goats were tested with the PCR. All ruminants were infected with known SRLV strains of the A1, A5, A12, A13, A16, A17, A18, A23, A24, A27, B1 and B2 subtypes.
RESULTS
A total of 69 (80.2%, 95% confidence interval 71.6%-88.8%) out of 86 tested samples gave positive results in the PCR. In 17 out of the 86 (19.8%) samples, no proviral DNA of SRLV was detected. The differentiation between MVV (genotype A) and CAEV (genotype B) by PCR matched the predating phylogenetic analysis invariably. No cross-reactivity was observed. On the other hand, the proportion of samples genotyped the same by the older phylogenetic analysis and the Eradikit SRLV Genotyping ELISA was 42.3%. The test was unable to classify 40.2% of samples, and 17.5% of sera were incorrectly classified.
CONCLUSION
Our results showed that the Eradikit SRLV genotyping kit is not a reliable method for predicting SRLV genotype, while the nested real-time PCR based on the LTR- region did prove to be, at least for genotypes A and B.
PubMed: 38947158
DOI: 10.2478/jvetres-2024-0025 -
CNS Neuroscience & Therapeutics Jul 2024Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its...
OBJECTIVE
Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics.
METHODS
This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones.
RESULTS
The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms.
CONCLUSIONS
These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.
Topics: Humans; Male; Female; Middle Aged; Aged; Adult; Wallerian Degeneration; Pons; Brain Stem Infarctions; Middle Cerebellar Peduncle; Magnetic Resonance Imaging; Neuroimaging
PubMed: 38946709
DOI: 10.1111/cns.14828 -
Echo Research and Practice Jul 2024Aortic stenosis (AS) is the most common degenerative valve disease in high income countries. While hemodynamic metrics are commonly used to assess severity of stenosis,...
BACKGROUND
Aortic stenosis (AS) is the most common degenerative valve disease in high income countries. While hemodynamic metrics are commonly used to assess severity of stenosis, they are impacted by loading conditions and stroke volume and are often discordant. Anatomic valve assessments such as aortic valve calcification (AVC) and valve motion (VM) during transthoracic echocardiography (TTE) can offer clues to disease severity. The reliability of these semi-quantitatively assessed anatomic imaging parameters is unknown.
METHODS
This is a retrospective study of semi-quantitative assessment of AVC and valve VM on TTE. TTEs representing a range of AS severities were identified. The degree of calcification of the aortic valve and the degree of restricted VM were assessed in standard fashion. AVC scores and valve motion were assessed by readers with varied training levels blinded to the severity of AS. Correlation and inter-reader reliability between readers were assessed.
RESULTS
420 assessments (210 each for AVC and VM) were collected for 35 TTEs. Correlation of AVC for imaging trainees (fellows and students, respectively), ranged from 0.49 (95% CI 0.18-0.70) to 0.62 (95% CI 0.36-0.79) and 0.58 (95% CI 0.30-0.76) to 0.54 (95% CI 0.25-0.74) for VM. Correlation of anatomic assessments between echocardiographer-assigned AVC grades was r = 0.76 (95% CI 0.57-0.87)). The correlation between echocardiographer-assigned assessment of VM was r = 0.73 (95% CI 0.53-0.86), p < 0.00001 for both. For echocardiographer AVC assessment, weighted kappa was 0.52 (0.32-0.72), valve motion weighted kappa was 0.60 (0.42-0.78).
CONCLUSION
There was good inter-reader correlation between TTE-based semi-quantitative assessment of AVC and VM when assessed by board certified echocardiographers. There was modest inter-reader reliability of semi-quantitative assessments of AVC and VM between board certified echocardiographers. Inter-reader correlation and reliability between imaging trainees was lower. More reliable methods to assess TTE based anatomic assessments are needed in order to accurately track disease progression.
CLINICAL TRIAL NUMBER
STUDY00003100.
PubMed: 38946008
DOI: 10.1186/s44156-024-00050-3 -
Bratislavske Lekarske Listy 2024True aneurysm of the radial artery is very rare. Aneurysmal expansion of arteries due to degenerative changes, possibly infections, primarily affects the abdominal and...
True aneurysm of the radial artery is very rare. Aneurysmal expansion of arteries due to degenerative changes, possibly infections, primarily affects the abdominal and thoracic aorta, intra and extracranial sections of cerebral arteries, popliteal artery, and visceral arteries. Published literature does not address the aneurysm on the distal sections of the arteries of upper or lower limb. Unlike the classic symptoms of aneurysmally altered arteries such as rupture, thrombosis and embolization, we encounter more often vascular compression syndrome in distal peripheral aneurysms. We demonstrate the case management of a patient with over 20 years increasing wrist resistance. A fusiform aneurysm of the distal section of the radial artery was identified by sonography. Under general anesthesia, we performed aneurysm resection and artery reconstruction using an interpositum from the ipsilateral cephalic vein. The histological examination of the resected tissue confirmed the presence of all three layers of the vascular wall, confirming the true aneurysm of the radial artery. No complications developed in the patient in the postoperative period and all problems related to the aneurysm subsided (Fig. 4, Ref. 23). Keywords: aneurysm, arteria radialis, surgical reconstruction.
Topics: Humans; Aneurysm; Radial Artery; Male; Syndrome; Middle Aged; Upper Extremity; Female
PubMed: 38943502
DOI: 10.4149/BLL_2024_64