Spinal Cord Stimulation Trial Electrodes Rapidly Produce Epidural Scarring, Impeding Surgical Paddle Lead Placement.

OBJECTIVES: After a successful percutaneous cylindrical electrode five-to-seven-day trial of spinal cord stimulation, subsequent permanent surgical paddle lead (SPL) placement can be impeded by epidural scar induced by the trial leads (TLs). Our goal was to determine whether a delay between TL and subsequent SPL placement provokes enhanced epidural scarring with an increased need for laminotomy extension required for scar removal for optimal SPL placement. MATERIALS AND METHODS: Using a prospectively maintained data base, a single-facility/surgeon retrospective study identified 261 patients with newly placed thoracolumbar SPLs from June 2013 to November 2023. Data were obtained from the patients' charts, including, but not limited to, timing between TL and SPL, operative time, and need for extension of laminotomy. RESULTS: We found that the need for laminotomy extension due to TL epidural scarring and longer operative times was not required in our patients if the SPL was placed within ten days of placement of the TL (0/26), leading to shorter operative times in those with SPL placed after ten days (122.42 ± 10.72 minutes vs 140.75 ± 4.72 minutes; p = 0.005). We found no association with other medical comorbidities that may be confounding factors leading to epidural scarring/extension of laminotomy or association with level of SPL placement, size of the spinal canal, or indication for SPL placement. CONCLUSIONS: TL placement leads to scarring in the epidural space that appears to mature after ten days of its placement. In approximately 34% of patients, this leads to prolonged operative time owing to the need for extension of laminotomy and subsequent clearing of epidural scar for optimal SPL placement.

STIM1 a calcium sensor promotes the assembly of an ECM that contains Extracellular vesicles and factors that modulate mineralization.

Osteoblasts and odontoblasts, are non-excitable cells and facilitate mass calcium transport during matrix mineralization. A sophisticated Ca2+ sensing mechanism is used to maintain Ca2+ homeostasis. STIM1 (Stromal interaction molecule 1) is a calcium sensor protein localized in the ER membrane and maintains calcium homeostasis by initiating the store-operated Ca2+ entry (SOCE) process, following store depletion. The role of STIM1 in dentin mineralization is yet to be elucidated. Therefore, transgenic DPSCs were generated in which overexpression or knockdown of STIM1 was achieved to study its function in matrix mineralization. Gene expression analysis and Alizarin Red staining assay demonstrated upregulation of genes involved in odontogenic differentiation and matrix mineralization with increased calcium deposition with STIM1 overexpression. Topology of the ECM examined by Field Emission Scanning Electron Microscopy (FESEM) showed the presence of large amounts of extracellular microvesicles with mineral deposits. Interestingly, silencing STIM1 resulted in fewer vesicles and less mineral deposits in the ECM. Analysis of the dentin-pulp complex of STIM1- deficient mice by micro-CT show reduced dentin thickness, malformed and highly porous alveolar bone, suggesting a cell intrinsic role for STIM1 in dentin mineralization. Confocal microscopy showed that DMP1-mediated depletion of store Ca2+ resulted in aggregation or "puncta-formation" of STIM1 at the plasma membrane indicative of a gating arrangement with Orai1 for Ca2+ influx. Together, our data provide evidence for an important role for STIM1 in dentin and alveolar bone mineralization by influencing intracellular Ca2+ oscillations that could provide signals for a wide array of cellular functions. STATEMENT OF SIGNIFICANCE: Calcium signaling and transport are fundamental to bone and dentin mineralization. Osteoblasts and odontoblasts transport large amounts of Ca2+ to the extracellular matrix. These cells maintain calcium homeostasis by spatially distributed calcium pumps and channels at the plasma membrane. STIM1 an ER Ca2+ sensor protein is an important component of the store-operated calcium entry (SOCE) process. In this study, we examined the role of STIM1 during the differentiation of dental pulp stem cells into functional odontoblasts and formation of mineralized dentin matrix. Stimulation of these cells with DMP1, a key regulatory protein in matrix mineralization, stimulates STIM1-mediated release of ER Ca2+ and SOCE activation. Silencing of STIM1 impairs signaling events, release of exosomes containing matrix proteins and matrix mineralization.

Adaptations to cursoriality and digit reduction in the forelimb of the African wild dog (Lycaon pictus).

BACKGROUND: The African wild dog (Lycaon pictus), an endangered canid native to southern and eastern Africa, is distinct among canids in being described as entirely tetradactyl and in its nomadic lifestyle and use of exhaustive predation to capture its prey instead of speed, strength, or stealth. These behavioral and morphological traits suggest a potentially unique set of adaptations. METHODS: Here, we dissected the forelimbs of an adult male L. pictus specimen and performed detailed descriptions and quantitative analyses of the musculoskeletal anatomy. RESULTS: Statistical comparisons of muscle masses and volumes revealed that L. pictus has relatively smaller wrist rotators (mm. pronator teres, pronator quadratus, supinator) than any other included carnivoran taxon, suggesting adaptive pressures for antebrachial stability over rotatory movement in the carpus of L. pictus. While a complete digit I is absent in L. pictus, a vestigial first metacarpal was discovered, resulting in changes to insertions of mm. extensor digiti I et II, abductor (et opponens) digiti I and flexor digiti I brevis. Mm. anconeus, brachialis and flexor carpi ulnaris caput ulnare all have more extensive origins in L. pictus than other canids suggesting an emphasis on posture and elbow stability. M. triceps brachii caput laterale has a larger origin in L. pictus and m. triceps brachii caput longum has an additional accessory head. Electromyographic studies have shown this muscle is active during the stance phase of trotting and galloping and is important for storing elastic energy during locomotion. We interpret these differences in size and attachments of muscles in L. pictus as adaptations for long distance running in this highly cursorial species, likely important for exhaustive predation. Absence of a full digit I in L. pictus may increase speed and stride length; however, the retention of a vestigial digit permits the attachment of reduced pollical muscles which may provide additional stability and proprioception to the carpus.

The ER Ca2+ sensor STIM1 can activate osteoblast and odontoblast differentiation in mineralized tissues.

Bone and dentin development requires temporal and spatial deposition of calcium phosphate mineral. A host of proteins works in concert to contribute to this tightly regulated process while malfunction in this scheme often leads to pathological defects. We have reported earlier that DMP1 stimulation of preosteoblasts leads to calcium release from internal Ca2+ stores and this store depletion is sensed by the ER Ca2+ sensor STIM1 (stromal interaction molecule 1). In this study, we first assessed the temporal and spatial localization of STIM1 protein during the development of bone and dentin by immunohistochemical methods. We further analyzed the function of STIM1 by establishing a stable MC3T3-E1 cell-line by overexpressing STIM1 (MC3T3-E1/STIM1 OE). Under mineralizing conditions, STIM1 overexpressing cells showed increased calcium deposits with higher expression of key osteogenic markers, such as Runx2 and type I collagen, BMP4 when compared with the control cells. Our results demonstrate that during mineralized matrix formation STIM1, the key ER sensor protein, can promote cellular differentiation in the presence of extracellular calcium.