Compression Injury Research Articles

Early decompression promotes motor recovery after cervical spinal cord injury in rats with chronic cervical spinal cord compression

The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4–5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.

An Injectable Rapid‐Adhesion and Anti‐Swelling Adhesive Hydrogel for Hemostasis and Wound Sealing

AbstractInjectable hydrogel adhesives integrating both rapid adhesion to wet tissues and anti‐swelling in humid environments are highly desired for fast hemostasis and wound sealing in surgical applications. Herein, utilizing the synergistic effect of thermo‐sensitive shrinkable nano‐micelle gelators and small molecular adhesive moieties, an injectable hydrogel with rapid‐adhesion and anti‐swelling properties (RAAS hydrogel) is fabricated. The RAAS hydrogel can undergo ultrafast gelation to achieve wet adhesion within 2 s of ultraviolet illumination and exhibit an outstanding anti‐swelling performance with non‐expansion of volume during the whole degradation process. It also presents good biocompatibility and low risk of hemolysis. Its fast hemostasis is demonstrated in diverse hemorrhage models with injuries in the liver, artery, heart, cranial vessel, and brain cortex in small animals. Importantly, its volume stability in humid internal environment can maintain the strong adhesion strength and avoid compression injury to spinal cord when applied for dura sealing. These data suggest that the injectable RAAS hydrogel holds potential for the applications of fast hemostasis and wound sealing with the benefits of stable adhesion and reducing the risk of tissue compression injury.

Elevated intraspinal pressure drives edema progression after acute compression spinal cord injury in rabbits

Elevated intraspinal pressure (ISP) following traumatic spinal cord injury (tSCI) can be an important factor for secondary SCI that may result in greater tissue damage and functional deficits. Our present study aimed to investigate the dynamic changes in ISP after different degrees of acute compression SCI in rabbits with closed canals and explore its influence on spinal cord pathophysiology. Closed balloon compression injuries were induced with different inflated volumes (40 μl, 50 μl or no inflation) at the T7/8 level in rabbits. ISP was monitored by a SOPHYSA probe at the epicenter within 7 days post-SCI. Edema progression, spinal cord perfusion and damage severity were evaluated by serial multisequence MRI scans, somatosensory evoked potentials (SEPs) and behavioral scores. Histological and blood spinal cord barrier (BSCB) permeability results were subsequently analyzed. The results showed that the ISP waveforms comprised three peaks, significantly increased after tSCI, peaked at 72 h (21.86 ± 3.13 mmHg) in the moderate group or 48 h (31.71 ± 6.02 mmHg) in the severe group and exhibited “slow elevated and fast decreased” or “fast elevated and slow decreased” dynamic changes in both injured groups. Elevated ISP after injury was correlated with spinal cord perfusion and edema progression, leading to secondary lesion enlargement. The secondary damage aggravation can be visualized by diffusion tensor tractography (DTT). Moreover, the BSCB permeability was significantly increased at the epicenter and rostrocaudal segments at 72 h after SCI; by 14 days, notable permeability was still observed at the caudal segment in the severely injured rabbits. Our results suggest that the ISP of rabbits with closed canals increased after acute compression SCI and exhibited different dynamic change patterns in moderately and severely injured rabbits. Elevated ISP exacerbated spinal cord perfusion, drove edema progression and led to secondary lesion enlargement that was strongly associated with BSCB disruption. For severe tSCI, early intervention targeting elevated ISP may be an indispensable choice to rescue spinal cord function.

850 Surgical Versus Non-Surgical Treatment of Unstable Lateral Compression Injuries of the Pelvis with Complete Sacral Fractures (LC1) in Non-Fragility Fracture Patients: A Systematic Review

Abstract Background Lateral compression type 1 (LC1) injuries comprise two-thirds of pelvic fractures. Approximately one third of LC1 fractures are unstable and may benefit from surgical fixation to improve stability but it is not clear if this leads to better clinical or cost-effectiveness outcomes. Method We performed a systematic review to determine whether surgical or non-surgical treatment yielded better clinical and cost-effectiveness for the treatment of unstable LC1 pelvic injuries with complete sacral fracture, excluding fragility fractures. We searched Medline, Embase and Cochrane databases from inception to June 2021, as well as clinical trials registries. Results Five observational studies met the inclusion criteria. 183 patients were treated surgically, and 314 patients treated non-surgically. Patients treated surgically had lower pain levels (Visual Analogue Scale) and fewer days to mobilisation. Quality of life (EQ-5D and SF-36 questionnaires) was better in the surgical group, but not statistically significant. No statistical differences in length of hospital stay or complication rates were found. Formal meta-analysis was not possible due to available study designs and heterogeneity. Conclusions This review highlights the low quantity and quality of existing data on patients with unstable LC1 pelvic fractures and the need for a definitive randomised controlled trial to determine whether surgical or non-surgical care should be the preferred treatment in terms of clinical and cost-effective care.

A Young Man With Acute-Onset Bilateral Arm Weakness After Traumatic Sciatic Neuropathy: A Clinical Vignette.

A Young Man With Acute-Onset Bilateral Arm Weakness After Traumatic Sciatic Neuropathy: A Clinical Vignette.

Factors Associated with Traumatic Diaphragmatic Rupture among Patients with Chest or Abdominal Injury: A Nationwide Study from Japan.

Background: Blunt traumatic diaphragmatic rupture (TDR) is a rare condition that is seen in patients with blunt thoracoabdominal trauma. However, factors that are associated with blunt TDR have not been fully revealed. The purpose of this study was to evaluate the factors that are associated with blunt TDR in trauma patients with a chest or abdominal injury using nationwide trauma registry data in Japan. Method: This study was a retrospective observational study with a 15-year study period from 2004 to 2018. We included trauma patients with a chest or abdominal Abbreviated Injury Score of two or more. We evaluated the relationship between confounding factors such as mechanism of injury and blunt TDR with multivariable logistic regression analysis. Results: This study included 65,110 patients, of whom 496 patients (0.8%) suffered blunt TDR. Factors that were associated with blunt TDR were disturbance of consciousness (adjusted OR [AOR]: 1.639, 95% CI: 1.326–2.026), FAST positive (AOR: 2.120, 95% CI: 1.751–2.567), front seat passenger (AOR: 1.748, 95% CI: 1.129–2.706), and compression injury by heavy object (AOR: 1.677, 95% CI: 1.017–2.765). Conclusion: This study revealed several factors that are associated with blunt TDR. The results of this study may be useful for clinicians when estimating blunt TDR.

Classification and morphology of hyperextension tibial plateau fracture.

This study was aimed at analyzing the incidence and characteristics of hyperextension tibial plateau fractures (HTPFs) by using a computed tomography (CT)-based "four-column and nine-segment" classification. In the coronal plane, HTPFs are divided into four types: pure hyperextension, hyperextension-varus, hyperextension-valgus, and hyperextension-bicondylar. Fractures in the sagittal plane were divided into three types: type 1, pure depression; type 2, cleavage extending to the posterior cortex with no displacement; and type 3, cleavage extending to the posterior cortex with a significant displacement. A retrospective analysis of CT images of the tibial plateau fractures from December 2007 to December 2021 was conducted. Fracture mapping was analyzed and drawn using the new classification system. A total of 136 (10.9%, 136/1253) fractures fulfilled the radiographic criteria for HTPF pattern in 136 knees (53.5 ± 13.3years). There were 11 knees with pure hyperextension fracture (8.1%), 23 with hyperextension-varus fracture (16.9%), 46 with hyperextension-valgus fracture (33.8%), and 56 with hyperextension-bicondylar fracture (41.2%) in the coronal plane. Furthermore, there were 64 (47.1%), 47 (34.6%), and 25 (18.4%) cases of type 1, type 2, and type 3 fractures, respectively, in the sagittal plane. In the three-dimensional heat map, the fracture lines were mainly located at the anterior rim of the tibial plateau, while the posterior articular surface was rarely involved. The main manifestations of HTPF are anterior compression and posterior avulsion injury. The CT-based four-column and nine-segment classification system could be used to categorize the injury characteristics of HTPF in the coronal and sagittal planes.

Intrathecal administration of naringenin improves motor dysfunction and neuropathic pain following compression spinal cord injury in rats: relevance to its antioxidant and anti-inflammatory activities.

BackgroundSpinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI.MethodsAnimals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups.ResultsNAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI.ConclusionsThese results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

Retraction Statement.

Retraction Statement.

Identifying small molecules for protecting chondrocyte function and matrix integrity after controlled compressive injury

ObjectiveArticular cartilage injury is central for the development of post-traumatic osteoarthritis (PTOA). With few disease-modifying therapies successful at offsetting progressive osteoarthritis (OA), our goal is to use a high throughput screening platform of cartilage injury to identify novel chondroprotective compounds. Targeting articular cartilage damage immediately after injury remains a promising therapeutic strategy to overcome irreversible tissue damage. MethodWe constructed a single impact-cartilage screening method using a multi-platen system that simultaneously impacts 48 samples and makes use of engineered cartilage tissue analogs (known as CTAs). Drug libraries were screened and assessed for their ability to alter two crucial biological responses to impact injuries, namely matrix degradation and cell stress. ResultsOver 500 small molecules were screened for their ability to alter proteoglycan loss, matrix metalloproteinase activity, and cell stress or death. Fifty-five compounds passed through secondary screening and were from commercial libraries of natural and redox, stem cell related compounds, as well as protease, kinase and phosphatase inhibitors. Through secondary screening, 16 promising candidates exhibited activity on one or more critical function of chondrocytes. While many are mechanistically known compounds, their function in joint diseases is not known. ConclusionThis platform was validated for screening drug activity against a tissue engineered model of PTOA. Multiple compounds identified in this manner have potential application as early protective therapy for treating PTOA, and require further study. We propose this screening platform can identify novel molecules that act on early chondrocyte responses to injury and provide an invaluable tool for therapeutic development.

Thoracic and lumbar spine trauma classification systems fail to predict post-traumatic kyphotic deformity

BackgroundPost-traumatic kyphosis of the thoracic and lumbar spine can lead to pain and decreased function. MRI has been advocated to assess ligament integrity and risk of kyphosis. MethodsAll thoracic and lumbar spine MRI performed for evaluation of trauma over a 3-year period at a single institution were reviewed. Patients were included if there was an MRI showing a vertebral body fracture and follow-up radiographs. Two observers retrospectively reviewed all radiographs, CT and MRI scans, and classified injuries based on the Denis, TLICS, AO and load sharing classification systems. Change in kyphosis between injury and follow-up studies was measured. The initial radiology reports made at time of patient injury were compared to the retrospective interpretations. ResultsThere were 67 separate injuries in 62 patients. Kyphosis measuring ≥ 10° developed despite an intact PLC in 6/14 nonoperative cases, and 3/7 surgically treated cases; when PLC was partially injured, it developed in 6/10 cases (8 treated nonoperatively, 2 treated operatively. Thirty injuries had complete disruption of PLC by MRI, 24 treated with fusion. Kyphosis ≥ 10° developed in 3/6 treated nonoperatively, and 8/24 treated with fusion. Development of kyphosis was independent of degree of vertebral body comminution. It developed equally in patients with Grade 2 and Grade 3 Denis injuries. It developed in patients with intact PLC when multiple vertebrae were involved and/or there was compressive injury to anterior longitudinal ligament (ALL). There was high interobserver variability in assessment of severity of ligamentous injury on MRI. ConclusionsClassification systems of thoracic and lumbar spine injury and integrity of the PLC failed to predict the risk of development of post-traumatic kyphotic deformity.

Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation.

Synaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We hypothesized that SynCAM3 may be related to the astrocytic scar (glial scar, the most important factor of CNS injury treatment) through extracellular matrix (ECM) reconstitution. Thus, we investigated the influence of the selective removal of SynCAM3 on the outcomes of spinal cord injury (SCI). SynCAM3 knock-out (KO) mice were subjected to moderate compression injury of the lower thoracic spinal cord using wild-type (WT) (C57BL/6JJc1) mice as controls. Single-cell RNA sequencing analysis over time, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and immunohistochemistry (IHC) showed reduced scar formation in SynCAM3 KO mice compared to WT mice. SynCAM3 KO mice showed improved functional recovery from SCI by preventing the transformation of reactive astrocytes into scar-forming astrocytes, resulting in improved ECM reconstitution at four weeks after injury. Our findings suggest that SynCAM3 could be a novel therapeutic target for SCI.

Treatment of Atlantoaxial Dislocation in Children with Down Syndrome Using Posterior Atlantoaxial Screw Fixation.

BackgroundTo investigate the effect of posterior atlantoaxial screw fixation for the treatment of atlantoaxial dislocation in children with Down syndrome (DS).MethodsChildren diagnosed with DS who underwent posterior atlantoaxial screw fixation or occipitocervical fusion from January 2017 to January 2020 in Hebei Children’s Hospital were retrospectively included. Preoperative CT and MRI were performed to check the os odontoideum (OsO) and spinal cord compression, signal changes and spinal cord injury grade (ASIA grade).ResultsAll 5 children have atlantoaxial dislocation and OsO. Among which 60% (3/5) of children had changes in spinal cord signals and 40% (2/5) had dural sac compression. Every child underwent posterior atlantoaxial screw fixation (3.5-mm diameter), and the average fusion level was 1.8 (1–2). All 5 cases wore the head-neck-chest brace for 3–6 months after the operation. 1 case had dural tear and recovered well after timely suturing. 1 case had internal fixation breakage of the prosthetic joint and underwent revision surgery. At the last follow-up, all cases were fused and the neurological function were all ASIA grade E.ConclusionAfter posterior atlantoaxial screw fixation, fusion and nerve recovery were achieved in all children with atlantoaxial dislocation and OsO. Postoperative head-neck-chest braces are necessary for children, especially those with occipitocervical fusion.

Voluntary exercise ameliorates neuropathic pain by suppressing calcitonin gene-related peptide and ionized calcium-binding adapter molecule 1 overexpression in the lumbar dorsal horns in response to injury to the cervical spinal cord

BackgroundNeuropathic pain (NP) is a frequent finding in patients diagnosed with spinal cord injuries (SCIs). To improve our understanding of the maladaptive changes taking place in the lumbar spinal cord that can lead to the development of NP and to find alternative options to treat this condition, we aimed to investigate the effects of voluntary exercise on NP after SCI and to elucidate its potential mechanisms. MethodsA rat model of post-SCI NP induced by compression of the posterior or lateral cervical spinal cord was used to evaluate the effects of voluntary exercise by measuring the bilateral withdrawal of the hind paws using the Von Frey filament and Hargreaves tests. The place escape/avoid paradigm was used to evaluate supraspinal pain processing and somatosensory evoked potentials (SEPs) were used to examine disturbances in proprioception. Locomotor function was evaluated using Basso, Beattie, and Bresnahan (BBB) scoring. Pathologic findings in hematoxylin and eosin-stained tissue and magnetic resonance imaging were used to evaluate the morphological changes after SCI. The lesion size within the cervical spinal cord was evaluated by staining with Eriochrome cyanine R. Quantitative polymerase chain reaction and immunohistochemistry were used to assess the expression of calcitonin gene-related peptide (CGRP) and ionized calcium-binding adapter molecule 1 (Iba-1) in the lumbar dorsal horns. ResultsAll injured rats developed mechanical hypersensitivity, hyposensitivity, and thermal hyperalgesia in the contralateral hind paws at 1 week post-injury. Rats that underwent lateral compression injury developed NP in the ipsilateral hind paws 1 week later than rats with a posterior compression injury. Our findings revealed that voluntary exercise ameliorated mechanical allodynia and thermal hyperalgesia, and significantly improved proprioception as measured by SEP, but had no impact on mechanical hypoalgesia or motor recovery and provided no significant neuroprotection after recovery from an acute SCI. SCI-induced NP was accompanied by increased expression of CGRP and Iba-1 in the lumbar dorsal horn. These responses were reduced in rats that underwent voluntary exercise. ConclusionsVoluntary exercise ameliorates NP that develops in rats after compression injury. Increased expression of CGRP and Iba-1 in the lumbar dorsal horns of rats exhibiting symptoms of NP suggests that microglial activation might play a crucial role in its development. Collectively, voluntary exercise may be a promising therapeutic modality to treat NP that develops clinically in response to SCI.

Raman spectroscopy and sciatic functional index (SFI) after low-level laser therapy (LLLT) in a rat sciatic nerve crush injury model.

Axonotmesis causes sensorimotor and neurofunctional deficits, and its regeneration can occur slowly or not occur if not treated appropriately. Low-level laser therapy (LLLT) promotes nerve regeneration with the proliferation of myelinating Schwann cells to recover the myelin sheath and the production of glycoproteins for endoneurium reconstruction. This study aimed to evaluate the effects of LLLT on sciatic nerve regeneration after compression injury by means of the sciatic functional index (SFI) and Raman spectroscopy (RS). For this, 64 Wistar rats were divided into two groups according to the length of treatment: 14days (n = 32) and 21days (n = 32). These two groups were subdivided into four sub-groups of eight animals each (control 1; control 2; laser 660nm; laser 808nm). All animals had surgical exposure to the sciatic nerve, and only control 1 did not suffer nerve damage. To cause the lesion in the sciatic nerve, compression was applied with a Kelly clamp for 6s. The evaluation of sensory deficit was performed by the painful exteroceptive sensitivity (PES) and neuromotor tests by the SFI. Laser 660nm and laser 808nm sub-groups were irradiated daily (100 mW, 40s, energy density of 133J/cm2). The sciatic nerve segment was removed for RS analysis. The animals showed accentuated sensory and neurofunctional deficit after injury and their rehabilitation occurred more effectively in the sub-groups treated with 660nm laser. Control 2 sub-group did not obtain functional recovery of gait. The RS identified sphingolipids (718, 1065, and 1440cm-1) and collagen (700, 852, 1004, 1270, and 1660cm-1) as biomolecular characteristics of sciatic nerves. Principal component analysis revealed important differences among sub-groups and a directly proportional correlation with SFI, mainly in the sub-group laser 660nm treated for 21days. In the axonotmesis-type lesion model presented herein, the 660nm laser was more efficient in neurofunctional recovery, and the Raman spectra of lipid and protein properties were attributed to the basic biochemical composition of the sciatic nerve.

Involvement of GABAA-rho Receptor in a Trigeminal Neuralgia Model

The antiepileptic drug carbamazepine is effective in a subpopulation of trigeminal neuralgia patients, in particular those suffering from pain associated with vascular compression of a trigeminal nerve. However, carbamazepine has failed in clinical trials for other neuropathic pain conditions, even those associated with peripheral nerve compression injuries. Carbamazepine is both a GABAA receptor (GAR) agonist and a blocker of voltage-gated Na+ channels (VGSC), and our recent data suggest that differences between trigeminal and somatic nerves with respect to the VGSC present are not sufficient to account for the therapeutic selectivity of carbamazepine. Therefore, we hypothesized that these observations reflected a differential involvement of GARs in somatic and trigeminal nerves. To test this, we employed a combination of electrophysiological and behavioral experiments in rat models of somatic (sciatic nerve, SN) and trigeminal (infraorbital nerve, ION) nerve compression (CCI). We observed that the potency of carbamazepine-induced compound action potential (CAP) block was increased by CCI of the ION but not the SN, and this increase in potency was reduced by the GAR blocker picrotoxin. The potency of the GAR agonist muscimol-induced block of the ION was greater than the SN, and CCI produced a further increase in efficacy. The GABAA-rho subunit mRNA and protein was increased by CCI of the ION, but not SN. The GABAA-rho receptor selective antagonist TPMPA reduced carbamazepine-induced CAP block of the ION. CCI was also associated with an increase in the potency of the GABAA-rho receptor preferring agonist TACA-induced block of the ION, but not SN. Finally, local administration of TACA to the ION but not SN, dose-dependently reversed CCI-induced mechanical sensitivity. Taken altogether, our results suggest GABAA-rho receptors are present and functional in ION, but not SN. This differential distribution of GABAA receptors could account for the therapeutic selectivity of carbamazepine for the treatment of TN. The work was supported by generous donations from TN patients and family members as well as NIH grant R01NS064988.

Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy.

Recently, marked therapeutic effects pertaining to the recovery of injured rat spinal cords (1 min compression injury of the sacrocaudal spinal cord (S2-Co1) resulting in tail paralysis) appeared after a single intraperitoneal administration of the stable gastric pentadecapeptide BPC 157 at 10 min post-injury. Besides the demonstrated rapid and sustained recovery (1 year), we showed the particular points of the immediate effect of the BPC 157 therapy that began rapidly after its administration, (i) soon after injury (10 min), or (ii) later (4 days), in the rats with a definitive spinal cord injury. Specifically, in counteracting spinal cord hematoma and swelling, (i) in rats that had undergone acute spinal cord injury, followed by intraperitoneal BPC 157 application at 10 min, we focused on the first 10–30 min post-injury period (assessment of gross, microscopic, and gene expression changes). Taking day 4 post-injury as the definitive injury, (ii) we focused on the immediate effects after the BPC 157 intragastric application over 20 min of the post-therapy period. Comparable long-time recovery was noted in treated rats which had definitive tail paralysis: (iii) the therapy was continuously given per orally in drinking water, beginning at day 4 after injury and lasting one month after injury. BPC 157 rats presented only discrete edema and minimal hemorrhage and increased Nos1, Nos2, and Nos3 values (30 min post-injury, (i)) or only mild hemorrhage, and only discrete vacuolation of tissue (day 4, (ii)). In the day 4–30 post-injury study (iii), BPC 157 rats rapidly presented tail function recovery, and no demyelination process (Luxol fast blue staining).

SU16f inhibits fibrotic scar formation and facilitates axon regeneration and locomotor function recovery after spinal cord injury by blocking the PDGFR\u03b2 pathway

BackgroundExcessively deposited fibrotic scar after spinal cord injury (SCI) inhibits axon regeneration. It has been reported that platelet-derived growth factor receptor beta (PDGFRβ), as a marker of fibrotic scar-forming fibroblasts, can only be activated by platelet-derived growth factor (PDGF) B or PDGFD. However, whether the activation of the PDGFRβ pathway can mediate fibrotic scar formation after SCI remains unclear.MethodsA spinal cord compression injury mouse model was used. In situ injection of exogenous PDGFB or PDGFD in the spinal cord was used to specifically activate the PDGFRβ pathway in the uninjured spinal cord, while intrathecal injection of SU16f was used to specifically block the PDGFRβ pathway in the uninjured or injured spinal cord. Immunofluorescence staining was performed to explore the distributions and cell sources of PDGFB and PDGFD, and to evaluate astrocytic scar, fibrotic scar, inflammatory cells and axon regeneration after SCI. Basso Mouse Scale (BMS) and footprint analysis were performed to evaluate locomotor function recovery after SCI.ResultsWe found that the expression of PDGFD and PDGFB increased successively after SCI, and PDGFB was mainly secreted by astrocytes, while PDGFD was mainly secreted by macrophages/microglia and fibroblasts. In addition, in situ injection of exogenous PDGFB or PDGFD can lead to fibrosis in the uninjured spinal cord, while this profibrotic effect could be specifically blocked by the PDGFRβ inhibitor SU16f. We then treated the mice after SCI with SU16f and found the reduction of fibrotic scar, the interruption of scar boundary and the inhibition of lesion and inflammation, which promoted axon regeneration and locomotor function recovery after SCI.ConclusionsOur study demonstrates that activation of PDGFRβ pathway can directly induce fibrotic scar formation, and specific blocking of this pathway would contribute to the treatment of SCI.

α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model.

α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid, has been reported to protect cells from oxidative stress damage by reacting with lysosomal iron and is more powerful than desferrioxamine (DFO). However, the role of LAP in experimental carotid artery intimal injury (CAII) has not yet been well investigated. Therefore, we sought to uncover the role and potential endovascular protective mechanisms of LAP in endothelial injury. In vitro, oxyhemoglobin (OxyHb) stimulation of cultured human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, balloon compression injury of the carotid artery was used to establish a rat CAII model. We found that the protein levels of cathepsin B/D, ferritin, transferrin receptor (TfR), cleaved caspase-3, and Bax increased in the injured endothelium and HUVECs but were rectified by DFO and LAP treatments, as revealed by western blotting and immunofluorescence staining. Additionally, DFO and LAP decreased oxidative stress levels and endothelial cell necrosis of the damaged endothelium. Moreover, DFO and LAP significantly ameliorated the increased oxidative stress, iron level, and lactic dehydrogenase activity of HUVECs and improved the reduced HUVEC viability induced by OxyHb. More importantly, DFO and LAP significantly reduced mitochondrial damage and were beneficial for maintaining lysosomal integrity, as indicated by acridine orange (AO), Lyso-Tracker Red, JC-1, and ATPB staining in HUVECs. Finally, LAP might offer more significant endovascular protective effects than DFO. Our data suggested that LAP exerted endovascular protective effects by inhibiting the apoptosis signaling pathway mediated by intralysosomal cathepsins by reacting with excessive iron in endothelial lysosomes after intimal injury.

Extrinsic Compression of Inflatable Penile Prosthesis Secondary to Prone Positioning for COVID-19 Pneumonia: A Case Series of Two Patients

IntroductionComplications of extrinsic compression on an inflatable penile prosthesis (IPP) due to prone positioning for COVID-19 pneumonia have not been described. Patients with an IPP present a unique challenge for managing compression injuries secondary to proning due to the dependent position of the penis and ability of the device to restrict blood flow to the distal penis when externally compressed for long periods of time. We present two patients with previous IPP placement who experienced glans and penile ischemia secondary to extrinsic compression of the penis from proning, who were monitored conservatively and avoided urgent explantation.ObjectiveTo describe two patients with IPPs who were intubated and proned for COVID-19 pneumonia who experienced IPP-related complications due to pressure injury, one of whom survived for follow-up.MethodsTwo male patients, ages 68 and 74 years, who developed penile injury following proning for COVID-19 pneumonia. The first patient presented with skin breakdown of the ventral aspect of the penis and scrotum without exposed implant. The second patient presented with a pale and dusky glans.ResultsThe first patient was managed by scrotal elevation with bacitracin application to the wound twice daily. There was no surgical intervention or debridement of the penile and scrotal wounds. The patient was then followed on an outpatient basis without need for explantation at 4-months from initial consultation (Figure 1). He underwent a CT of the abdomen and pelvis as well as a CT Urogram as an outpatient that confirmed appropriate positioning of all components of the device without evidence of underlying infection. On exam, the penile prosthesis was well-positioned and cycled normally, with a freely mobile pump within the scrotum. The second patient expired during hospitalization from COVID-19 respiratory failure, but was monitored for six days without glans necrosis (Figure 2) once external pressure was removed.ConclusionsPatients with IPPs who require prone positioning are a unique population that are at risk for extrinsic compression injury of the penis. In contrast to ischemia related to instrinsic compression, such as with the sliding technique, which results in glans necrosis and necessitates urgent explantation, conservative treatment and serial examination in the setting of external compression from prone intubation was a viable and safe option to immediate explantation in these patients. Prevention, in the form of proper padding and minimization of external compression, remains paramount as we obtain more long term data from this unique patient population.DisclosureNo