Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.

Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 µg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.

Optimal allocation of physicians improves accessibility and workload disparities in stroke care.

BACKGROUND: Inequalities in access to stroke care and the workload of physicians have been a challenge in recent times. This may be resolved by allocating physicians suitable for the expected demand. Therefore, this study analyzes whether reallocation using an optimization model reduces disparities in spatial access to healthcare and excessive workload. METHODS: This study targeted neuroendovascular specialists and primary stroke centers in Japan and employed an optimization model for reallocating neuroendovascular specialists to reduce the disparity in spatial accessibility to stroke treatment and workload for neuroendovascular specialists in Japan. A two-step floating catchment area method and an inverted two-step floating catchment area method were used to estimate the spatial accessibility and workload of neuroendovascular specialists as a potential crowdedness index. Quadratic programming has been proposed for the reallocation of neuroendovascular specialists. RESULTS: The reallocation of neuroendovascular specialists reduced the disparity in spatial accessibility and the potential crowdedness index. The standard deviation (SD) of the demand-weighted spatial accessibility index improved from 125.625 to 97.625. Simultaneously, the weighted median spatial accessibility index increased from 2.811 to 3.929. Additionally, the SD of the potential crowdedness index for estimating workload disparity decreased from 10,040.36 to 5934.275 after optimization. The sensitivity analysis also showed a similar trend of reducing disparities. CONCLUSIONS: The reallocation of neuroendovascular specialists reduced regional disparities in spatial accessibility to healthcare, potential crowdedness index, and disparities between facilities. Our findings contribute to planning health policies to realize equity throughout the healthcare system.

Spatial-temporal analysis of cerebral infarction mortality in Hokkaido, Japan: an ecological study using a conditional autoregressive model.

BACKGROUND: Accessibility to stroke treatments is a challenge that depends on the place of residence. However, recent advances in medical technology have improved health outcomes. Nevertheless, the geographic heterogeneity of medical resources may increase regional disparities. Therefore, evaluating spatial and temporal influences of the medical system on regional outcomes and advanced treatment of cerebral infarction are important from a health policy perspective. This spatial and temporal study aims to identify factors associated with mortality and to clarify regional disparities in cerebral infarction mortality at municipality level. METHODS: This ecological study used public data between 2010 and 2020 from municipalities in Hokkaido, Japan. We applied spatial and temporal condition autoregression analysis in a Bayesian setting, with inference based on the Markov chain Monte Carlo simulation. The response variable was the number of deaths due to cerebral infarction (ICD-10 code: I63). The explanatory variables were healthcare accessibility and socioeconomic status. RESULTS: The large number of emergency hospitals per 10,000 people (relative risk (RR) = 0.906, credible interval (Cr) = 0.861 to 0.954) was associated with low mortality. On the other hand, the large number of general hospitals per 10,000 people (RR = 1.123, Cr = 1.068 to 1.178) and longer distance to primary stroke centers (RR = 1.064, Cr = 1.014 to 1.110) were associated with high mortality. The standardized mortality ratio decreased from 2010 to 2020 in Hokkaido by approximately 44%. Regional disparity in mortality remained at the same level from 2010 to 2015, after which it narrowed by approximately 5% to 2020. After mapping, we identified municipalities with high mortality rates that emerged in Hokkaido's central and northeastern parts. CONCLUSION: Cerebral infarction mortality rates and the disparity in Hokkaido improved during the study period (2010-2020). This study emphasized that healthcare accessibility through places such as emergency hospitals and primary stroke centers was important in determining cerebral infarction mortality at the municipality level. In addition, this study identified municipalities with high mortality rates that require healthcare policy changes. The impact of socioeconomic factors on stroke is a global challenge, and improving access to healthcare may reduce disparities in outcomes.

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature.

A 17-year-old female complained of lower extremity pain that progressed to low back pain accompanied by paraparesis. Magnetic resonance imaging revealed a mass in the conus medullaris of the spinal cord at the thoracic spine 11-12 level. The patient underwent resection of the mass. The pathological diagnosis was anaplastic astrocytoma based on the densely proliferating astrocytic tumor cells without necrosis or microvascular proliferation. The patient received chemoradiotherapy with oral temozolomide and a total of 54 Gy of local irradiation, followed by 24 courses of temozolomide as maintenance chemotherapy. The patient survived for 8 years without tumor recurrence following the initial treatment. Genetic analysis of the tumor revealed a BRAF V600E mutation that has not yet been reported in spinal cord high-grade gliomas (HGGs). In recent years, the molecular therapy targeting the BRAF V600E mutation has been applied in clinical practice for several cancer types. Although the frequency in spinal cord HGGs is uncertain, it is necessary to investigate BRAF V600E mutation as a potential therapeutic target in the future.

[A Case of Positional Vertebral Artery Occlusion due to Physiological Cervical Extension with Occipital Condylar Spur].

Positional vertebral artery occlusion(PVAO)is a mechanical occlusion of the extracranial vertebral artery(VA)due to physiological movement of the head and neck. However, only a few cases of mechanical VA compression due to routine flexion-extension of the neck have been reported. We present a unique case of PVAO due to neck extension with an occipital condylar spur. A 78-year-old man was admitted to our hospital for sudden onset of right hemiparesis and dysarthria. Magnetic resonance imaging(MRI)revealed bilateral occipital and cerebellar infarctions and vessel occlusion extending from the VA to the basilar artery. Mechanic thrombectomy resulted in partial recanalization. Computed tomography angiography(CTA)performed the next day showed spontaneously recanalized left VA with some wall irregularity. CTA in the neck-extended position revealed a severely compressed left VA in its V3 segment, which was attributed to the left occipital condylar spur with degenerative changes of the condyle-C1 facet. Cervical MRI also showed a pseudotumor from the lower clivus to the odontoid process that indicated mechanical stress on the occipitocervical ligaments. An occiput to C2 fusion was performed to stabilize and avoid dynamic vascular compression. Postoperative CTA revealed no evidence of restricted flow with flexion or extension movements of the neck. It should be noted that physiological head and neck movements accompanied by condylar degenerative changes could be a cause of vertebrobasilar insufficiency.

Estimation of the number of feeding arteries of spinal arteriovenous malformations by using three-dimensional digital subtraction angiography.

PURPOSE: Spinal angiography is the gold standard for evaluation or diagnosis of spinal arteriovenous malformations (AVMs). However, some feeding arteries might be overlooked when multiple feeders exist. This study aimed to retrospectively review cases of spinal intra-dural AVMs, which were identified by three-dimensional digital subtraction angiography (3D-DSA), and attempted to estimate the number of feeding arteries. METHODS: We retrospectively reviewed patients with spinal intra-dural AVMs who underwent 3D-DSA at Hokkaido University Hospital from January 2005 to December 2016. We selected 9 patients in whom we could obtain data of multi-planar reconstruction of 3D-DSA. We measured the computed tomography (CT) values of feeding arteries and draining veins. The CT values represented the averages of maximum CT values of 5 continuous axial slices. The ratio of the CT value of feeders to that of drainers (F/D ratio) was calculated. The correlation between the F/D ratio and the number of feeders was examined with Pearson's correlation coefficient. RESULTS: The average number of feeders was 2.3 (1-4), and the number of feeders was significantly positively correlated with the F/D ratio (r = 0.855, P = .003). CONCLUSIONS: We conclude that the number of feeding arteries of spinal intra-dural AVMs can be estimated by using the F/D ratio obtained from 3D-DSA. These slides can be retrieved under Electronic Supplementary Material.

Subarachnoid Hemorrhage with Progressive Cerebral Steno-Occlusive Disease: Report of 2 Cases.

Nontraumatic nonaneurysmal subarachnoid hemorrhage (SAH) is a rare condition. Among them, SAH with cerebral steno-occlusive disease is quite rare. Moreover there has been no report of SAH patient who had been diagnosed with steno-occlusive disease since before. We here report 2 cases of nontraumatic nonaneurysmal convexity SAH who originally had progressive cerebral steno-occlusive disease. Case 1, a woman in her 40s who had diagnosed left internal carotid artery (ICA) stenosis 6 years before complained of headache. She was diagnosed SAH and progressive ICA stenosis, then performed revascularization. Case 2, a woman in her 40s who had diagnosed right ICA stenosis 7 months before complained of headache. She was diagnosed with SAH and ICA occlusion. These 2 cases suggested that progressive cerebral steno-occlusive disease lead to SAH due to collapse of their fragile pial anastomoses.

[Utility of Intraoperative Catheter Myelography during Intrathecal Baclofen Pump Implantation:Report of 2 Cases].

We report two patients in whom the intrathecal baclofen(ITB)catheter was located in the subdural space, although we had confirmed good outflow of spinal fluid from the spinal catheter. Patient 1 was a woman in her 30s with spastic quadriplegia due to subarachnoid hemorrhage. An ITB pump was implanted, and a good outflow of spinal fluid from the spinal catheter was observed during the surgery. Postoperatively, her spasticity did not improve. Catheter myelography revealed that the spinal catheter was located in the subdural space. Using intraoperative catheter myelography, we corrected the position of the catheter. Patient 2 was a man in his 20s diagnosed with adrenoleukodystrophy. An ITB therapy was performed to improve his spastic gait. Intraoperative catheter myelography showed that the spinal catheter was located in the subdural space, although there was good outflow of spinal fluid from the catheter. Our experience suggests that the outflow of spinal fluid alone should not be used to determine the location of the spinal catheter. Intraoperative catheter myelography is useful for the correct placement of the spinal catheter in the subarachnoid space.

[A Dumbbell-Type Thoracic Spinal Lipoma: A Case Report].

Spinal lipomas are rare, accounting for less than 1% of all spinal tumors. Most are associated with spinal dysraphism. Spinal lipomas without spinal dysraphism are uncommon;they are typically subpial tumors. Some tumors are located both inside and outside the dura mater (so-called "dumbbell-type"). Herein, we report a patient with a dumbbell-type thoracic spinal lipoma. A man in his 50's complained of progressive gait disturbance, dysesthesia in his left leg, and hyperesthesia in his right leg. His symptoms were worsened by exercise. CT and MRI revealed a thoracic spinal lipoma extending from the spinal cord to the intervertebral foramen at the Th 6-8 level. He underwent partial tumor removal and untethering. Postoperatively he reported gradual symptom abatement. Dumbbell-type spinal lipomas are very rare. Besides partial removal of the tumor, untethering should be considered when symptoms are associated with tethering of the spinal cord.

[Efficacy of Stent-Assisted Coil Embolization for a Dissecting Aneurysm of the Cervical Internal Carotid Artery Caused by a Systemic Vascular Disease: A Case Report].

Systemic vascular diseases such as fibromuscular dysplasia, Ehlers-Danlos syndrome, Marfan syndrome, and Behçet's disease are known to cause spontaneous dissecting aneurysms of the cervical internal carotid artery. These diseases are generally associated with vascular fragility; therefore, invasive treatments are avoided in many cases of dissecting aneurysms, and a conservative approach is used for the primary disease. Surgical or intravascular treatment may be chosen when aneurysms are progressive or are associated with a high risk of hemorrhage; however, there is no consensus on which treatment is better. We report a case of a dissecting aneurysm of the cervical internal carotid artery in a patient with suspected Behçet's disease, which was treated using stent-assisted coil embolization. A man in his 40's, with suspected Behçet's disease, presented with an enlarged dissecting aneurysm of the right cervical internal carotid artery. The lesion was present for approximately 10 years. We performed stent-assisted coil embolization for the lesion. Post-surgery, no aneurysms were detected with carotid artery echography. Our case report suggests that stent-assisted coil embolization is a promising treatment for dissecting aneurysms of the cervical internal carotid artery. In addition, the procedure demonstrates the utility of carotid artery echograms for examining recanalization after stent-assisted coil embolization.

Optimal Transport System for Acute Ischemic Stroke Patients: A Cost-Effectiveness Analysis.

This study conducted cost utility analysis comparing 4 systems of transporting acute ischemic stroke patients in Hokkaido, Japan. Hypothetical patients were generated on a geographic information system, and their outcomes were estimated according to their transport time to hospitals administering tissue plasminogen activator and/or endovascular thrombectomy. The transport systems where a neurointerventionist traveled for earlier endovascular thrombectomy were most cost-effective in some rural areas, while direct transportation to comprehensive stroke centers was more cost-effective in other areas.

Stem Cell Therapies for Intracerebral Hemorrhage: Review of Preclinical and Clinical Studies.

Despite recent developments in the treatments for ischemic stroke, such as tissue plasminogen activator (t-PA) and thrombectomy, effective therapies for intracerebral hemorrhage (ICH) remain scarce. Stem cell therapies have attracted considerable attention owing to their potential neuro-regenerative ability; preclinical and clinical studies have been conducted to explore strategies for achieving functional recovery following ICH. In this review, we summarize the findings of preclinical studies on stem cell therapies of ICH, with a focus on different animal models, stem cell sources, transplantation methods, and their potential mechanisms of action. We also provide an overview of data from clinical trials to discuss the current status and future perspectives. Understanding the effectiveness and limitations of stem cell therapy and the future prospects could expand the applications of this novel therapeutic approach for ICH.

The Prediction of Neurological Prognosis for Cervical Spondylotic Myelopathy Using Diffusion Tensor Imaging.

OBJECTIVE: Although cervical spondylotic myelopathy (CSM) can be easily diagnosed using magnetic resonance imaging (MRI), prediction of surgical effect using preoperative radiological examinations remains difficult. In previous studies, it was reported that diffusion tensor imaging (DTI) may be used for the prediction of surgical effect; however, these studies did not consider the influences of spinal cord compression even though the values of DTI indexes can be distorted by compressive lesions in patients with CSM. Therefore, it is uncertain whether preoperative DTI indexes can actually predict the surgical effect. The aim of this study was to investigate DTI metrics that are hardly affected by spinal cord compression and can accurately predict neurological status after decompressive surgery. METHODS: Twenty-one patients with CSM who underwent surgery and 10 healthy volunteers were enrolled in this study. The subjects underwent cervical MRI, and values of DTI indexes including axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were recorded at each intervertebral level. Further, the Japanese Orthopaedic Association (JOA) score of each patient with CSM was recorded before and after surgery for neurological status evaluation. Preoperative and postoperative values of DTI indexes were compared, and correlations between preoperative DTI parameters and postoperative neurological recovery were assessed. RESULTS: After surgery, the lesion-adjacent (LA) ratios of RD and ADC increased (p = 0.04 and p = 0.062, respectively), while the LA ratio of FA decreased (p = 0.075). In contrast, the LA ratio of AD hardly changed. A negative correlation was observed between preoperative LA ratio of AD and JOA recovery rate 6 months after surgery (r = -0.379, p = 0.091). Based on preoperative LA ratio of AD, the patients were divided into a low AD group and a high AD group, and JOA recovery rate 6 months after surgery was found to be higher in the low AD group than in the high AD group (p = 0.024). CONCLUSION: In patients with CSM, preoperative LA ratio of AD is seldom affected by spinal cord compression, and it negatively correlates with JOA recovery rate 6 months after surgery.

Predicting Mechanical Thrombectomy Outcome and Time Limit through ADC Value Analysis: A Comprehensive Clinical and Simulation Study Using Machine Learning.

Predicting outcomes after mechanical thrombectomy (MT) remains challenging for patients with acute ischemic stroke (AIS). This study aimed to explore the usefulness of machine learning (ML) methods using detailed apparent diffusion coefficient (ADC) analysis to predict patient outcomes and simulate the time limit for MT in AIS. A total of 75 consecutive patients with AIS with complete reperfusion in MT were included; 20% were separated to test data. The threshold ranged from 620 × 10-6 mm2/s to 480 × 10-6 mm2/s with a 20 × 10-6 mm2/s step. The mean, standard deviation, and pixel number of the region of interest were obtained according to the threshold. Simulation data were created by mean measurement value of patients with a modified Rankin score of 3-4. The time limit was simulated from the cross point of the prediction score according to the time to perform reperfusion from imaging. The extra tree classifier accurately predicted the outcome (AUC: 0.833. Accuracy: 0.933). In simulation data, the prediction score to obtain a good outcome decreased according to increasing time to reperfusion, and the time limit was longer among younger patients. ML methods using detailed ADC analysis accurately predicted patient outcomes in AIS and simulated tolerance time for MT.

Access to mechanical thrombectomy and ischemic stroke mortality in Japan: a spatial ecological study.

Background: Advances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions. Methods: We used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk. Results: The median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor's degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido. Conclusion: Access to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor's degrees or above are at risk of death from stroke.

Fatal case of subdural empyema caused by Campylobacter rectus and Slackia exigua.

We report a fatal subdural empyema caused by Campylobacter rectus in a 66-year-old female who developed acute onset of confusion, dysarthria, and paresis in her left extremities. A CT scan showed hypodensity in a crescentic formation with a mild mid-line shift. She had a bruise on her forehead caused by a fall several days before admission, which initially raised subdural hematoma (SDH) diagnosis, and a burr hole procedure was planned. However, her condition deteriorated on the admission night, and she died before dawn. An autopsy revealed that she had subdural empyema (SDE) caused by Campylobacter rectus and Slackia exigua. Both microorganisms are oral microorganisms that rarely cause extra-oral infection. In our case, head trauma caused a skull bone fracture, and sinus infection might have expanded to the subdural space causing SDE. CT/MRI findings were not typical for either SDH or SDE. Early recognition of subdural empyema and prompt initiation of treatment with antibiotics and surgical drainage is essential for cases of SDE. We present our case and a review of four reported cases.

Preoperative dorsal disc height is a predictor of indirect decompression effect through oblique lateral interbody fusion in lumbar degenerative stenosis.

The extent of indirect decompression after oblique lateral interbody fusion (OLIF) is one of the most important factors in deciding the strategy. To assess the radiographical predictors of the effect of indirect decompression in patients with lumbar degenerative spondylosis by OLIF. Thirty-two consecutive patients who underwent OLIF at 58 lumbar disc levels were enrolled in this study. The radiographic measurements included central disc height (cDH), dorsal disc height (dDH), right/left foraminal height in sagittal plane computed tomography (CT), and cross-sectional dural sac antero-posterior diameter (CDSD) in axial plane CT. All patients were followed up for 1 year after surgery. All CT parameters (cDH, dDH, CDSD, right foraminal height [RFH], and left foraminal height [LFH]) significantly increased after OLIF (P < .0001). The mean raised height difference was 4.3, 3.4, 3.4, and 2.6 mm for cDH, dDH, RFH, and LFH, respectively. The mean CDSD increase was 1.4 mm. The median values of post/pre-operation (change rates) were 1.5 times in cDH, 1.9 times in dDH, and 1.2 times in CDSD, RFH, and LFH. RFH and LFH change rates were related with both cDH and dDH change rates, while the CDSD change rate was only associated with the dDH change rate (P = .0206*) but not with cDH (P = .2061). There was a significant negative relationship between the CDSD change rate and preoperative dDH (P = .0311*, R2 = 0.0817) but not with preoperative cDH (P = .4864). OLIF should be avoided for patients with preserved high dDH.

Efficacy of Two-Stage Surgery for Spinal Cord Ependymomas.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to elucidate cases for which staged surgeries are effective by a retrospective review of previous operative cases of spinal ependymomas. OVERVIEW OF LITERATURE: Patients with spinal ependymomas are expected to have a good prognosis following total resection. However, forcible dissection of spinal ependymomas will lead to neurological deterioration. Moreover, resection is sometimes difficult when the tumor is large. We have performed two-stage surgeries for large spinal ependymomas, but the indication of staged surgery is unclear. METHODS: We retrospectively reviewed patients diagnosed with spinal ependymomas who underwent tumor resection in our institution. We obtained data regarding patients' clinical characteristics, tumoral radiological characteristics, and surgical factors and compared them to clear prognostic factors. Two-stage surgery was performed in 11 patients (36.7%), and single surgery was performed in 19 patients (63.3%). RESULTS: Thirty patients were included in the analyses and divided into two groups: single surgery and two-stage surgery groups. In the single surgery group, high tumor-cord ratio (TCR) and intraoperative motor evoked potential (MEP) reduction were significantly correlated with unfavorable outcomes, which were defined as deterioration of the modified McCormick scale grades 2 months and 1 year postoperatively. Alternatively, these factors were not significantly correlated with postoperative unfavorable outcomes in the two-stage surgery group. Receiver operating characteristic curves indicated that TCR of 0.866 yielded 85.7% sensitivity and 83.3% specificity 2 months postoperatively. CONCLUSIONS: The results suggested that high TCR might be an indication of two-stage surgery and that its cutoff value is 0.866. Moreover, switching from single surgery to two-stage surgery may prevent postoperative neurological deterioration when intraoperative MEP is decreasing.

Intravenous transplantation of amnion-derived mesenchymal stem cells promotes functional recovery and alleviates intestinal dysfunction after spinal cord injury.

Spinal cord injury (SCI) is often accompanied by gastrointestinal dysfunction due to the disconnection of the spinal autonomic nervous system. Gastrointestinal dysfunction reportedly upregulates intestinal permeability, leading to bacterial translocation of the gut microbiome to the systemic circulation, which further activates systemic inflammation, exacerbating neuronal damage. Mesenchymal stem cells (MSC) reportedly ameliorate SCI. Here, we aimed to investigate their effect on the associated gastrointestinal dysfunction. Human amnion-derived MSC (AMSCs) were intravenously transplanted one day after a rat model of midthoracic SCI. Biodistribution of transplanted cells, behavioral assessment, and histological evaluations of the spinal cord and intestine were conducted to elucidate the therapeutic effect of AMSCs. Bacterial translocation of the gut microbiome was examined by in situ hybridization and bacterial culture of the liver. Systemic inflammations were examined by blood cytokines, infiltrating immune cells in the spinal cord, and the size of the peripheral immune tissue. AMSCs released various neurotrophic factors and were mainly distributed in the liver and lung after transplantation. AMSC-transplanted animals showed smaller spinal damage and better neurological recovery with preserved neuronal tract. AMSCs transplantation ameliorated intestinal dysfunction both morphologically and functionally, which prevented translocation of the gut microbiome to the systemic circulation. Systemic inflammations were decreased in animals receiving AMSCs in the chronic phase. Intravenous AMSC administration during the acute phase of SCI rescues both spinal damage and intestinal dysfunction. Reducing bacterial translocation may contribute to decreasing systemic inflammation.

Intracerebral Transplantation of Mesenchymal Stromal Cell Compounded with Recombinant Peptide Scaffold against Chronic Intracerebral Hemorrhage Model.

Background: Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model. Methods: Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action. Results: rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization. Conclusion: Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.