Cascade Of Degeneration Research Articles

Towards Early Diagnosis and Screening of Alzheimer's Disease Using Frequency Locked Whispering Gallery Mode Microtoroid Biosensors.

Alzheimer's disease (AD) is a progressive form of dementia affecting almost 55 million people worldwide. It is characterized by the abnormal deposition of amyloid plaques and neurofibrillary tangles within the brain, leading to a pathological cascade of neuron degeneration and death as well as memory loss and cognitive decline. Amyloid beta (Aβ) is an AD biomarker present in cerebrospinal fluid and blood serum and correlates with the presence of amyloid plaques and tau tangles in the brain. Measuring the levels of Aβ can help with early diagnosis of AD, which is key for studying novel AD drugs and delaying the symptoms of dementia. However, this goal is difficult to achieve due to the low levels of AD biomarkers in biofluids. Here we demonstrate for the first time the use of FLOWER (frequency locked optical whispering evanescent resonator) for quantifying the levels of post-mortem cerebrospinal fluid (CSF) Aβ42 in clinicopathologically classified control, mild cognitive impairment (MCI), and AD participants. FLOWER is capable of measuring CSF Aβ42 (area under curve, AUC = 0.92) with higher diagnostic performance than standard ELISA (AUC = 0.82) and was also able to distinguish between control and MCI samples. Our results demonstrate the capability of FLOWER for screening CSF samples for early diagnosis of Alzheimer's pathology.

A nerve-wracking buzz: lessons from Drosophila models of peripheral neuropathy and axon degeneration.

The degeneration of axons and their terminals occurs following traumatic, toxic, or genetically-induced insults. Common molecular mechanisms unite these disparate triggers to execute a conserved nerve degeneration cascade. In this review, we will discuss how models of peripheral nerve injury and neuropathy in Drosophila have led the way in advancing molecular understanding of axon degeneration and nerve injury pathways. Both neuron-intrinsic as well as glial responses to injury will be highlighted. Finally, we will offer perspective on what additional questions should be answered to advance these discoveries toward clinical interventions for patients with neuropathy.

Oligodendrocyte death initiates synchronous remyelination to restore cortical myelin patterns in mice.

Myelin degeneration occurs in neurodegenerative diseases and aging. In these conditions, resident oligodendrocyte progenitor cells (OPCs) differentiate into oligodendrocytes that carry out myelin repair. To investigate the cellular dynamics underlying these events, we developed a noninflammatory demyelination model that combines intravital two-photon imaging with a single-cell ablation technique called two-photon apoptotic targeted ablation (2Phatal). Oligodendrocyte 2Phatal in both sexes results in a myelin degeneration cascade that triggers rapid forms of synchronous remyelination on defined axons. This remyelination is driven by oligodendrocytes differentiated from a subset of morphologically distinct, highly branched OPCs. Moreover, remyelination efficiency depends on the initial myelin patterns, as well as the age of the organism. In summary, using 2Phatal, we show a form of rapid synchronous remyelination, mediated by a distinct subset of OPCs, capable of restoring the original myelin patterning in adulthood but not aging.

The association between vertebral endplate defects, subchondral bone marrow changes, and lumbar intervertebral disc degeneration: a retrospective, 3-year longitudinal study.

To investigate the influence of vertebral endplate defects and subchondral bone marrow changes on the development of lumbar intervertebral disc degeneration (DD). Patients > 18 y/o without any history of lumbar fusion who had repeat lumbar magnetic resonance imaging scans primarily for low back pain (LBP) performed at a minimum of 3years apart at a single institution, and no spinal surgery in between scans were included. Total endplate score (TEPS), Modic changes (MC), and Pfirrmann grading (PFG) per lumbar disc level were assessed. DD was defined as PFG ≥ 4. Three hundred and fifty-three patients (54.4% female) were included in the final analysis, comprising 1765 lumbar intervertebral discs. The patient population was 85.6% Caucasian with a median age of 60.1years and a body mass index (BMI) of 25.8kg/m2. A cutoff score of 5 was identified for the TEPS above which both the prevalence of DD and the odds of developing DD increased. The probability of developing DD did not differ significantly between lumbar disc levels (P = 0.419). In the multivariable analysis with adjustments for age, sex, race, body mass index (BMI), MC, TEPS cutoff > 5, and spinal level, only age (OR = 1.020; P = 0.002) was found to be an independent risk factor for developing intervertebral DD. Our results suggest that TEPS does not unequivocally predict intervertebral DD in patients with LBP, since higher degrees of endplate defects might also develop secondarily to DD, and MC tend to occur late in the cascade of degeneration.

Establishment and Application of a Novel In Vitro Model of Microglial Activation in Traumatic Brain Injury.

Mechanical impact-induced primary injury after traumatic brain injury (TBI) leads to acute microglial pro-inflammatory activation and consequently mediates neurodegeneration, which is a major secondary brain injury mechanism. However, the detailed pathologic cascades have not been fully elucidated, partially because of the pathologic complexity in animal TBI models. Although there are several in vitro TBI models, none of them closely mimic post-TBI microglial activation. In the present study, we aimed to establish an in vitro TBI model, specifically reconstituting the pro-inflammatory activation and associated neurodegeneration following TBI. We proposed three sets of experiments. First, we established a needle scratch injured neuron-induced microglial activation and neurodegeneration in vitro model of TBI. Second, we compared microglial pro-inflammatory cytokines profiles between the in vitro TBI model and TBI in male mice. Additionally, we validated the role of injured neurons-derived damage-associated molecular patterns in amplifying microglial pro-inflammatory pathways using the in vitro TBI model. Third, we applied the in vitro model for the first time to characterize the cellular metabolic profile of needle scratch injured-neuron-activated microglia, and define the role of metabolic reprogramming in mediating pro-inflammatory microglial activation and mediated neurodegeneration. Our results showed that we successfully established a novel in vitro TBI model, which closely mimics primary neuronal injury-triggered microglial pro-inflammatory activation and mediated neurodegeneration after TBI. This in vitro model provides an advanced and highly translational platform for dissecting interactions in the pathologic processes of neuronal injury-microglial activation-neuronal degeneration cascade, and elucidating the detailed underlying cellular and molecular insights after TBI.SIGNIFICANCE STATEMENT Microglial activation is a key component of acute neuroinflammation that leads to neurodegeneration and long-term neurologic outcome deficits after TBI. However, it is not feasible to truly dissect primary neuronal injury-induced microglia activation, and consequently mediated neurodegeneration in vivo Furthermore, there is currently lacking of in vitro TBI models closely mimicking the TBI primary injury-mediated microglial activation. In this study, we successfully established and validated a novel in vitro TBI model of microglial activation, and for the first time, characterized the cellular metabolic profile of microglia in this model. This novel microglial activation in vitro TBI model will help in elucidating microglial inflammatory activation and consequently associated neurodegeneration after TBI.

Graphene-collagen cryogel controls neuroinflammation and fosters accelerated axonal regeneration in spinal cord injury.

Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function. The pathology of SCI is multifaceted and involves a cascade of events, including neuroinflammation and neuronal degeneration at the epicenter, limiting repair process. We developed a supermacroporous, mechanically elastic, electro-conductive, graphene crosslinked collagen (Gr-Col) cryogels for the regeneration of the spinal cord post-injury. The effects of graphene in controlling astrocytes reactivity and microglia polarization are evaluated in spinal cord slice organotypic culture and rat spinal cord lateral hemisection model of SCI. In our work, the application of external electric stimulus results in the enhanced expression of neuronal markers in an organotypic culture. The implantation of Gr-Col cryogels in rat thoracic T9-T11 hemisection model demonstrates an improved functional recovery within 14days post-injury (DPI), promoted myelination, and decreases the lesion volume at the injury site. Decrease in the expression of STAT3 in the implanted Gr-Col cryogels may be responsible for the decrease in astrocytes reactivity. Microglia cells within the implanted cryogels shows higher anti-inflammatory phenotype (M2) than inflammatory (M1) phenotype. The higher expression of mature axonal markers like β-tubulin III, GAP43, doublecortin, and neurofilament 200 in the implanted Gr-Col cryogel confirms the axonal regeneration after 28 DPI. Gr-Col cryogels also modulate the production of ECM matrix, favouring the axonal regeneration. This study shows that Gr-Col cryogels decreases neuroinflammation and accelerate axonal regeneration.

Patient with Lumbar Spondylosis and Diskogenic Pain

Diskogenic low back pain (LBP), defined as pain that originates from a damaged vertebral disk, is a common cause of LBP. It is characterized by a three-phase cascade of degeneration marked by dysfunction, instability, and stabilization. A distinct pathologic characteristic of the disks from patients with diskogenic LBP has been found to be the formation of the zones of vascularized granulation tissue, with extensive innervation extending from the outer layer of the annulus fibrosus into the nucleus pulposus along a torn fissure. In addition, there appears to be an association between microbial infection and symptomatic disk degeneration. Low-virulence microorganisms, in particular Propionibacterium acnes, might be causing a chronic low-grade infection in the lower intervertebral disks in some patients. The diagnosis of diskogenic pain is primarily based on clinical manifestations, physical examinations, imaging studies, and provocative diskography. Diskogenic pain should be differentiated from other axial back pain conditions, such as facet arthropathy, sacroiliac joint pain, myofascial strain and pain, vertebral compression fracture, and other, less common conditions. Treatment options should be tailored to individual needs. Early and gradual physical and behavioral therapies are encouraged. Pharmacologic therapy, composed primarily of analgesics, nonsteroidal antiinflammatory drugs, muscle relaxants, and antidepressants, may have modest positive effects. A subset of patients with Modic type I changes in magnetic resonance imaging may benefit antibiotic therapy directed at the infected disks by P. acnes and other low-virulence microorganisms. There is evidence that supports the use of epidural steroid injections and intradiskal injections (methylene blue, ozone, steroids) for diskogenic pain. Additional options include intradiskal biacuplasty, gray ramus communicans nerve blocks/radiofrequency ablation, and intradiskal stem cell injections for disk repair/regeneration, all of which have gained support in clinical trials. These treatment modalities have shown promise to provide equal or even better outcomes compared with surgical spinal fusion or total disk replacement with an artificial disk. This review contains 2 figures and 149 references. Keywords: collagen, diskogenic low back pain (LBP), herniation, intervertebral disk, spondylosis

Neuronal Hyperexcitability and Free Radical Toxicity in Amyotrophic Lateral Sclerosis: Established and Future Targets.

Amyotrophic lateral sclerosis (ALS) is a devastating disease with evidence of degeneration involving upper and lower motor neuron compartments of the nervous system. Presently, two drugs, riluzole and edaravone, have been established as being useful in slowing disease progression in ALS. Riluzole possesses anti-glutamatergic properties, while edaravone eliminates free radicals (FRs). Glutamate is the excitatory neurotransmitter in the brain and spinal cord and binds to several inotropic receptors. Excessive activation of these receptors generates FRs, inducing neurodegeneration via damage to intracellular organelles and upregulation of proinflammatory mediators. FRs bind to intracellular structures, leading to cellular impairment that contributes to neurodegeneration. As such, excitotoxicity and FR toxicities have been considered as key pathophysiological mechanisms that contribute to the cascade of degeneration that envelopes neurons in ALS. Recent advanced technologies, including neurophysiological, imaging, pathological and biochemical techniques, have concurrently identified evidence of increased excitability in ALS. This review focuses on the relationship between FRs and excitotoxicity in motor neuronal degeneration in ALS and introduces concepts linked to increased excitability across both compartments of the human nervous system. Within this cellular framework, future strategies to promote therapeutic development in ALS, from the perspective of neuronal excitability and function, will be critically appraised.

Is there an interdependence between paraspinal muscle mass and lumbar disc degeneration? A MRI based study at 2520 levels in 504 patients

IntroductionLow back pain is one of the most common cause for outpatient visits. Though few studies have shown the vital role of paraspinal muscles in lumbar spine pathology, literature is scarce regarding the influence of the paraspinal muscles in disc degeneration. We aimed to analyse the correlation between paraspinal muscles and disc degeneration. MethodsThis is a Level III Prospective Cohort Study done in MRI of lumbosacral spine in 504 patients at 2520 levels from L1-2 to L5-S1. The parameters assessed were age, Pfirrmann grade for disc degeneration and paraspinal muscle (Multifidus and Erector Spinae) mass assessed by the gross cross sectional area of the muscle.The values and their correlation was analyzed using SPSS software. ResultsThe study included a total of 504 patients (231 males and 273 females) with a mean age of 52.00 ± 15.00 (22–80) years. The mean GCSA in cm2 of the paraspinal muscles at L1-L2, L2-L3,L3-L4,L4-L5,L5-S1 were 16.177 ± 2.72, 17.275 ± 2.16, 16.900 ± 3.07, 16.800 ± 2.63, 13.426 ± 2.42 respectively. We found that the age of the patient is directly proportional to the disc degeneration and inversely proportional to GCSA of paraspinal muscle. There was a significant negative correlation between disc degeneration and paraspinal muscle mass. ConclusionWe found that the paraspinal muscle mass reduces and Pfirrman's Grade increases as age advances. Also patients with disc degeneration tend to have wasting of paraspinal muscles and vice versa. Hence, strengthening the paraspinal muscles should be emphasised to prevent back pain and to stall the degeneration cascade.

Breast cancer related upper limb lymphedema: approach and surgical management.

Lymphedema of the upper extremities in a common, chronic, progressive and debilitating disease, that affects the increasing population of cancer survivors. The gold standard is nowadays an integrated approach, including conservative and surgical treatment. Lymphatic surgery, particularly the physiologic procedures including lymphatic-venous anastomosis and vascularized lymph node transfer, should be offered to lymphedema patients as soon as possible, aimed to ameliorate the subjective symptoms and to interrupt the degeneration cascade that makes this condition progressive over time. Indications for surgery, patient selection, and diagnostic tools will be discussed.

3D analysis of fatty infiltration of the paravertebral lumbar muscles using T2 images-a new approach.

Factors influencing paraspinal muscle degeneration are still not well understood. Fatty infiltration is known to be one main feature of the degeneration cascade. The aim of this cross-sectional study was to illustrate the 3D cluster of paraspinal lumbar muscle degeneration on T2-weighted MRI images using our newly developed software application 'iSix'. Mono- (Mm. rotatores), multi- (Mm. multifidus) and pluri-segmental (M. erector spinae) lumbar muscles groups were segmented on T2-weighted MR sequences using a novel computer-assisted technique for quantitative muscle/fat discrimination. The degree of fatty infiltration of the three predefined muscle groups was compared on a 3-dimensional basis, with regard to segment involvement and age. General linear models were utilized for statistical comparison. N = 120 segments (age: 52.7; range 16-87years) could be included. The overall relative fatty infiltration of the mono-segmental muscles was higher (21.1 14.5%) compared to the multi-segmental (16.0 8.8% p = 0.049) and pluri-segmental muscles (8.5 8.0%; p = 0.03). Mono-segmental muscles on the levels L4/5 (22.9 ± 10.2 [CI 17.6-28.2] %) and L5/S1 (27.01 ± 15.1 [CI 21.4-32.7] %) showed a significant higher amount of fat compared to the levels L2/3 (8.2 ± 6.8 [CI 2.2-14.2] %; L4/5 vs. L2/3, p = 0.03; L5/S1 vs. L2/3, p = 0.02) and L3/4 (13.2 ± 5.4 [CI 8.6-17.7]%; L4/5 vs. L3/4, p = 0.02; L5/S1 vs. L3/4, p < 0.01). Multivariate linear regression analyses revealed age and Pfirrmann grade as independent factors for fatty muscle degeneration. 3D analysis of fatty infiltration is an innovative tool to study lumbar muscle degeneration. Mono-segmental muscles are more severely affected by degeneration compared to multi-/pluri-segmental muscles, especially at the L4/5 and L5/S1 level. Age and disc degeneration independently correlate with muscle degeneration.

Propionibacterium acnes Accelerates Intervertebral Disc Degeneration by Inducing Pyroptosis of Nucleus Pulposus Cells via the ROS-NLRP3 Pathway.

Our previous study verified the occurrence of Propionibacterium acnes (P. acnes), a low-virulence anaerobic bacterium, latently residing in degenerated intervertebral discs (IVDs), and the infection had a strong association with IVD degeneration. We explored whether P. acnes induces nucleus pulposus cell (NPC) pyroptosis, a more dangerous cell death process than apoptosis, and accelerates IVD degeneration via the pyroptotic products interleukin- (IL-) 1β and IL-18. After coculturing with P. acnes, human NPCs showed significant upregulation of NOD-like receptor 3 (NLRP3), cleaved IL-1β, cleaved caspase-1, and cleaved gasdermin D in response to the overexpression of IL-1β and IL-18 in a time- and dose-dependent manner. In addition, the gene expression of inflammatory factors and catabolic enzymes significantly increased in normal NPCs when cocultured with pyroptotic NPCs in a transwell system, and the adverse effects were inhibited when NPC pyroptosis was suppressed. Furthermore, inoculation of P. acnes into the IVDs of rats caused significant pyroptosis of NPCs and remarkable IVD degeneration. Finally, coculture of NPCs with P. acnes induced the overexpression of reactive oxygen species (ROS) and NLRP3, while inhibition of both factors reduced NPC pyroptosis. Therefore, P. acnes induces NPC pyroptosis via the ROS-NLRP3 signaling pathway, and the pyroptotic NPCs cause an IVD degeneration cascade. Targeting the P. acnes-induced pyroptosis of NPCs may become an alternative treatment strategy for IVD degeneration in the future.

Degenerate cascade fluorescence: Optical spectral-line narrowing via a single microwave cavity* *Project supported by the National Natural Science Foundation of China (Grants Nos. 61875067 and 61178021).

For a three-level atom, two nondegenerate (even microwave and optical) electric dipole transitions are usually allowed; for either of these, the fluorescence spectra are well-described in terms of spontaneous transitions from a triplet of dressed sublevels to an adjacent lower-lying triplet. When the three dressed sublevels are equally spaced from each other, a remarkable feature known as degenerate cascade fluorescence takes place, which displays a five-peaked structure. We show that a single cavity can make all the spectral lines extremely narrow, whether they arise from cavity-coupled or cavity-free transitions. This effect is based on intrinsic cascade lasing feedback and makes it possible to use a single microwave cavity (even a bad cavity) to narrow the spectral lines in the optical frequency regime.

Morphological study of the retina of WAG/Rij rats with pigmentary degeneration in postnatal ontogenesis

The aim of the study was to detect morphofunctional features of the retina of WAG/Rij rats during postnatal development from the 1st to the 360th day after birth.Material and methods. The study included retina of the inbred WAG/Rij rats (60 eyeballs from 30 rats totally) from the 1st to the 360th day of life. Standard histological studies were performed on paraffin sections stained with hematoxylin and eosin. Immunohistochemical method was used to determine the expression of acidic glial fibrillar protein GFAP in the rat retina. Mouse monoclonal antibodies (Santa Cruz Biotechnology) and a universal secondary detection system (NovocastraTM) were used for imaging. The degree of protein expression in the retina of WAG/Rij rats was compared in different age groups.Results. It was found that after birth, the retina of rat models of the WAG/Rij line is formed in the same way as the retina of rats of other strains and acquires a definitive structure only by the end of the second week (correlates with the opening of the eyes). On the 20th day, the first signs of dystrophic and destructive processes appear in the retina of WAG / Rij rats progressing as they grow older and leading to retinal gliosis. The increase in the expression of acidic glial fibrillar protein GFAP begins from the 30th day and increases with age as destructive processes in the retina increase. Conclusion. The early postnatal development of the retina of the WAG/Rij rats, which correlates in character with the postnatal retina development of rats of other strains, is interrupted by the launch of destructive processes in the retina soon after its complete differentiation. The further intensifying cascade of degeneration over time leads to the death of retinal neurons and their replacement by glial cells.

Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha.

Inflammation plays an important role in the pathogenesis of intervertebral disc (IVD) degeneration. The proinflammatory cytokine tumor necrosis factor alpha (TNF‐α) has shown markedly higher expression in degenerated human disc tissue compared with healthy controls. Anti‐inflammatory treatment targeting TNF‐α has shown to alleviate discogenic pain in patients with low back pain. Therefore, in vitro and ex vivo inflammatory models utilizing TNF‐α provide relevant experimental conditions for drug development in disc degeneration research.The current method article addressed several specific questions related to the model establishment.(a) The effects of bovine and human recombinant TNF‐α on bovine nucleus pulposus (NP) cells were compared. (b) The required dose for an inflammatory IVD organ culture model with intradiscal TNF‐α injection was studied. (c) The effect of TNF‐α blocking at different stages of inflammation was evaluated.Outcomes revealed that bovine and human recombinant TNF‐α induced equivalent inflammatory effects in bovine NP cells. A bovine whole IVD inflammatory model was established by intradiscal injection of 100 ng TNF‐α/ cm3 disc volume, as indicated by increased nitric oxide, glycosaminoglycan, interleukin 6 (IL‐6), and interleukin 8 (IL‐8) release in culture media, and upregulation of MMP3, ADAMTS4, IL‐8, IL‐6, and cyclooxygenase (COX)‐2 expression in NP tissue. However, results in human NP cells showed that the time point of anti‐inflammatory treatment was crucial to achieve significant effects. Furthermore, anticatabolic therapy in conjunction with TNF‐α inhibition would be required to slow down the pathologic cascade of disc degeneration.

Does Type II Diabetes Induce Early Senescence and Degeneration in Human Intervertebral Discs? A Tissue Biomarker Evaluation

Diabetes mellitus is one of the leading causes of morbidity resulting in multi-organ dysfunction. Animal studies have shown that hyperglycemia results in stress-induced senescence through the p16-pRb pathway, thereby accelerating early disc degeneration. There is a paucity of literature on the effect of hyperglycemia in human intervertebral disc cells. We aimed to analyze the effect of diabetes mellitus in human intervertebral disc cells. This is a prospective study done in patients with degenerative disc disease. Patients were categorized into a control group (no diabetes: 26 patients) and a study group (type 2 diabetes for > 3 years: 24 patients). All patients underwent either discectomy or transforaminal lumbar interbody fusion and the removed disc was transported to pathology department. Tissue was prepared and histopathological grading was done followed by immunohistochemistry studies using antibodies for MMP-1, p21, p16, and pRb. Samples from diabetic patients had severe (grade 2) degenerative changes compared with the control group (grade 1). Changes were more intense in the nucleus pulposus with increased cellularity and clustering of chondrocytes, and disorganization and loss of nuclear matrix. Immunohistochemical staining for MMP1, p16, and pRb was more intense (Q score = 4) whereas the staining for p21 was less intense (Q score = 1) in the diabetic group compared with the control group. Our study demonstrates that type 2 diabetes mellitus accelerates stress-induced senescence in human intervertebral discs resulting in early disc degeneration. Also, the severity of disc degeneration is severe compared with the normal subjects. Hyperglycemia can affect the intervertebral discs similar to other organs and hence adequate control of blood glucose in diabetics can prevent the disc degeneration, which is the initiator of degeneration cascade in spine.

Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys.

Cortical injury, such as injuries after stroke or age-related ischemic events, triggers a cascade of degeneration accompanied by inflammatory responses that mediate neurological deficits. Therapeutics that modulate such neuroinflammatory responses in the aging brain have the potential to reduce neurological dysfunction and promote recovery. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) are lipid-bound, nanoscale vesicles that can modulate inflammation and enhance recovery in rodent stroke models. We recently assessed the efficacy of intravenous infusions of MSC-EVs (24-h and 14-days post-injury) as a treatment in aged rhesus monkeys (Macaca mulatta) with cortical injury that induced impairment of fine motor function of the hand. Aged monkeys treated with EVs after injury recovered motor function more rapidly and more fully than aged monkeys given a vehicle control. Here, we describe EV-mediated inflammatory changes using histological assays to quantify differences in markers of neuroinflammation in brain tissue between EV and vehicle-treated aged monkeys. The activation status of microglia, the innate macrophages of the brain, is critical to cell fate after injury. Our findings demonstrate that EV treatment after injury is associated with greater densities of ramified, homeostatic microglia, along with reduced pro-inflammatory microglial markers. These findings are consistent with a phenotypic switch of inflammatory hypertrophic microglia towards anti-inflammatory, homeostatic functions, which was correlated with enhanced functional recovery. Overall, our data suggest that EVs reduce neuroinflammation and shift microglia towards restorative functions. These findings demonstrate the therapeutic potential of MSC-derived EVs for reducing neuroinflammation after cortical injury in the aged brain.

Trans-foraminal endoscopic uniportal decompression in degenerative lumbar spondylolisthesis: a technical and case report

BackgroundDegenerative spondylolisthesis is a common spinal pathology. Traditionally, spinal fusion is an accepted standard surgical treatment for listhesis. But fusion is a major intervention with its known pitfalls. With technological progression, minimally invasive spinal fusion (MISF) procedures are becoming mainstream. Percutaneous trans-foraminal endoscopic lumbar discectomy/decompressions (PTELD) without stabilization has many advantages over even a MISF for select group of patients.Case presentationIn this case report, we describe using a uniportal unilateral trans-foraminal approach (TFA) for stable listhesis with lumbar disc herniation (LDH) causing chronic bilateral radicular symptoms and back pain with acute exacerbation. Under local anesthesia, we used a flat entry for PTELD, which facilitates an approach to both disc sides ventrally and even dorsal aspect lateral recess decompression on the dominant ipsilateral side. No fixation was done. An excellent outcome is obtained immediately at 6 weeks and maintained at 39 months of follow-up.ConclusionPTELD is worth considering as an intermediate procedure before fusion is offered in lateral recess stenosis in stable listhesis patients who have consented and understand the progressive cascade of spinal degeneration.

Elevated expression of ICAM-1 in synovium is associated with early inflammatory response for cartilage degeneration in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is increasingly being recognized as an independent risk factor for the onset and progression of osteoarthritis (OA). Extensive studies have focused on the contribution of obesity (excessive mechanical stress), comorbidity frequently found in T2DM, to cartilage destruction during OA development. However, a little is known about how diabetes-related inflammation may affect the local cartilage in a diabetic objective. In the present study, we were able to establish a T2DM rat model using a combination of a low dose of streptozotocin with high-fat and high-sugar diet. Although the cartilage integrity was comparable between the control and T2DM groups, the expression of matrix metalloproteinases-13 (MMP-13) was significantly upregulated in T2DM, indicating the initiation of an early cascade of cartilage degeneration. In parallel, an obvious alteration of subchondral bone remodeling (inhibition of bone formation) was observed, as evidenced by the reduction of osterix-expressing positive cells. Moreover, we demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) in the serum and synovium of T2DM rats was elevated, accompanied by an increase of synovitis score. We also noticed that the number of F4/80-positive macrophage cells was significantly increased in the T2DM group. Mechanistically, the expression of ICAM-1 in fibroblast-like synoviocytes can be triggered by glucose and interleukin-1β, which are the two important factors within the joint of T2DM. Given that MMP-13 expression was significantly upregulated in the T2DM cartilage, and that ICAM-1-mediated filtration of macrophage was associated with synovitis, we propose that ICAM-1 is essential for triggering a vicious cycle of inflammation within the joint, whichtogether subsequently drivers the cartilage degradation.

Treatment of unstable knee osteochondritis dissecans in the young adult: results and limitations of surgical strategies-The advantages of allografts to address an osteochondral challenge.

Joint surface incongruence resulting from osteochondritis dissecans (OCD) alters the articular physiologic congruence, increasing the contact stress on adjacent joint surfaces and accelerating wear and the cascade of joint degeneration. Accordingly, the restoration of articular surface integrity is of major importance, especially in young adults where, in lesions left untreated or following simple fragment excision, early osteoarthritis can be anticipated. Therefore, the treatment algorithm in unstable knee OCD of the young adult foresees surgical options to restore the articular surface. Several procedures have been proposed, including refixation of the detached fragment bone marrow stimulation, osteochondral autograft implantation, fresh osteochondral allograft transplantation, and cell-based or cell-free regenerative techniques. The aim of this review was to summarize the evidence for these surgical strategies, reporting their results and limitations. The overall evidence documents positive results for each of the assorted surgical procedures applied to treat unstable OCD, thus indicating support for their selected use to treat osteochondral defects paying particular attention to their specific indications for the lesion characteristics. The fixation of a good quality fragment should be pursued as a first option, while unfixable small lesions may benefit from autografts. For large lesions, available cell-based or cell-free osteochondral scaffold are a feasible solution but with limitation in terms of regenerated tissue quality. In this light, fresh allografts may offer articular surface restoration with viable physiologic osteochondral tissue providing a predictably successful outcome, and therefore they may currently represent the most suitable option to treat unstable irreparable OCD lesion in young adults. LEVEL OF EVIDENCE: V.