The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protects against rTBI-induced long-term neurobehavioral disorders in rats via normalizing white matter integrity and gray matter microglial response. Rats were subjected to repeated mild lateral fluid percussion on day 0 and day 3. On the fourth day post-surgery, MSCs groups received MSCs (4 × 106 cells/ml/kg, intravenously) and were assessed by the radial maze, Y maze, passive avoidance tests, and modified neurological severity scores. Hematoxylin & eosin, and Luxol fast blue stainings were used to examine the histopathology and white matter thickness. At the same time, immunofluorescence staining was used to investigate the numbers of tumor necrosis factor-alpha (TNF-α)-containing microglia in gray matter. Three to nine months after neurotrauma, rats displayed sensorimotor and cognitive impairments, reduced thickness in white matter, and over-accumulation of TNF-α-containing microglia and cellular damage in gray matter. Therapy with BM-MSCs significantly attenuated the rTBI-induced sensorimotor and cognitive impairments and all their complications. Mesenchymal stem cell therapy might accelerate the recovery of sensorimotor and cognitive impairments in rats with rTBI via normalizing myelin integrity and microglia response.

We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day “0”) or repeated mild (1.5 atm on days “0” and “2”) traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1–9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

To determine the mechanisms underlying the beneficial effects of mesenchymal stem cells (MSC) on brain trauma-induced retinopathy both in vivo and in vitro . Repeated traumatic brain injury (TBI) was induced by lateral fluid percussion in adult male Wistar rats under general anesthesia. The sham and TBI groups received an intravenous dose of normal saline (1 mL/kg of body weight) or MSC (4 × 10 6 cells/ml/kg) on day 3 after surgery, respectively. The visual cliff method and modified neurological severity score were used to test the visual and neurobehavioral function of rats. Thirty-five days after TBI, rats were euthanized, and histochemical analyses were conducted. Cultured R28 cells were subjected to a stretch injury (SI) and then cocultured with MSC. The R28 cell viability, apoptosis, mitochondria membrane potential, radical oxygen species (ROS) generation, protein signaling, and growth factors composition were measured. Rats, 35 days post-TBI, displayed both visual disturbances and neurobehavioral deficits. Simultaneously, reduced RGC layer thickness, decreased cell numbers, increased RGC apoptosis, and decreased b-catenin-containing neurons were noted. Our in vitro studies further demonstrated that SI caused reduced cell viability, neuronal apoptosis and autophagy, mitochondria distress, increased intracellular ROS contents, and decreased b-catenin expression in cultured R28. Intravenous administration of MSC significantly ameliorated the visual disturbance and retinopathies in TBI rats. Topical application of MSC significantly attenuated stretch injury-induced cell stress responses in cultured RGC. MSC therapy might ameliorate visual disturbances and retinopathies in rats with neurotrauma via broad normalization of retinal b-catenin-related signaling pathways.

-BACKGROUND: The beneficial effect of pretreatment with statins on traumatic brain injury (TBI)-induced depression and anxiety and its mechanism of action remain -nclear. In this study, we combined epidemiological and experimental animal data to clarify this issue. -METHODS: We used the Taiwan National Health Insur-ance database to identify patients who were diagnosed with TBI from 2000 to 2013 and compared patients with and without statin treatment matched by age, sex, and under-lying comorbidities in a 1:1 ratio. The risk of developing depression and/or anxiety was compared between patients with and without a statin using Cox proportional hazards regression. We also used a rat model to assess the effect of lovastatin pretreatment on neurobehavioral and neuro-pathological changes following TBI.-RESULTS: The risk of developing depression was lower in the 41,803 patients in the statin cohort than nonstatin cohort (adjusted hazard ratio, 0.91 [95% confidence interval, 0.83-0.99]). In animal models, the lovastatin group had significantly reduced infarct volume, decreased immobility time and latency to eat, a reduced number of Fluoro-Jade -positive cells and levels of glial fibrillary acidic protein and tumor necrosis factor-alpha, and increased adenosine monophosphate-activated protein kinase (AMPK) and its u pstream kinase liver kinase B1 in the hippocampal dentate gyrus. These effects were blocked in AMPK inhibitor -pretreated TBI rats. -CONCLUSIONS: Our epidemiological data showed that a decreased risk of depression was associated with statin pretreatment, which was supported by an animal study. The u nderlying mechanism for this appears to involve AMPK activation in the statin pretreatment-induced alleviation of TBI.

The interrelationships between neuronal viability, synaptic integrity, and microglial responses remain in infancy. In dealing with the question, we induced a stretch injury to evaluate the mechanical effects of trauma on rat primary cortical neurons and BV2 microglial cells in a transwell culture system. The viability of primary neurons and BV2 cells was determined by MTT. Synaptic integrity was evaluated by determining the expression of beta-secretase 1 (BACE1), amyloid-beta (Aβ), microtubule-associated protein 2 (MAP2), and synaptophysin (vehicle protein). Both CD16/32-positive (CD16/32 + ) and CD206-positive (CD206 + ) microglia cells were detected by immunofluorescence staining. The phagocytic ability of the BV2 cells was determined using pHrodo E. coli BioParticles conjugates and flow cytometry. We found that stretch injury BV2 cells caused reduced viability and synaptic abnormalities characterized by Aβ accumulation and reductions of BACE1, MAP2, and synaptophysin in primary neurons. Intact BV2 cells exhibited normal phagocytic ability and were predominantly CD206 + microglia cells, whereas the injured BV2 cells exhibited reduced phagocytic ability and were predominantly CD16/32 + microglial cells. Like a stretch injury, the injured BV2 cells can cause both reduced viability and synaptic abnormalities in primary neurons; intact BV2 cells, when cocultured with primary neurons, can protect against the stretch-injured-induced reduced viability and synaptic abnormalities in primary neurons. We conclude that CD206 + and CD16/32 + BV-2 cells can produce neuroprotective and cytotoxic effects on primary cortical neurons.

Background Traumatic brain injury (TBI) has been reported as a risk factor for brain cancer development. However, the magnitude of the impact of TBI on systemic cancer development has not been clarified. Methods A retrospective longitudinal cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2011. A total of 35,306 patients were initially enrolled, and 14,795 patients with mild TBI and 14,795 patients with moderate/severe TBI were matched using the National Health Insurance Research Database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of TBI adjusted for potential confounding factors. Results After matching, the results showed that patients with moderate/severe TBI had a high mortality rate (17.7% vs. 10.4%) and shorter time interval from TBI to death (mean 3.6 years vs. 5.8 years). No differences were observed in cancer incidence (4.1% vs. 4.1%) or risk factors for mortality between mild and moderate/severe TBI patients. However, patients aged between 46 and 55 years, female patients, and patients with pre-existing renal disease had a significant higher cancer incidence risk in moderate/severe TBI compared with mild TBI patients. The top 15 most common cancers showed that mild TBI patients had a higher percentage of head and neck cancer. The overall mortality rate in all TBI patients diagnosed with cancer was about 50%, and the cancer-specific mortality is approximately 85% in death of TBI patients with cancer. Conclusions We concluded that the incidence risk of a new cancer diagnosis and mortality risk of TBI patients with cancer between the mild TBI and moderate/severe TBI patients were not significantly different.

Background Transforaminal Lumbar Interbody Fusion (TLIF) is commonly associated with higher complications and longer operative time. This study aims to evaluate the effectiveness, safety, and usability of a novel minimally invasive surgery (MIS) bone graft delivery device. Methods 73 consecutive patients with lumbar spondylosis, degenerative disc disease, spondylolisthesis, scoliosis or trauma were enrolled in this randomized controlled trial. Group 1 comprised 39 patients treated with the novel MIS bone graft delivery device. Group 2 consisted of 34 patients treated with the conventional system. The primary objective of the study was the assessment of the amount of bone graft delivery using the device. The secondary objectives were the effect of the device on operative time, pain relief, disability improvement, and bone fusion grade. Results Bone delivery amount was significantly higher in the MIS device group (6.7 ± 2.9 mL) compared to the conventional group (2.3 ± 0.5 mL), p < 0.001. Regarding the operation time, the MIS device group was associated significantly lower duration than the conventional group (p < 0.001). After a 3-month follow-up, 39.5% of the patients in the MIS device group and 3.5% of the patients in the conventional group were observed to achieve grade I fusion (complete fusion). There was a significant difference in fusion success rates (p < 0.01). Conclusion The novel MIS bone graft delivery device was associated with successful bone delivery. Our MIS device provides promising modality with less operative time and higher bone fusion rates than conventional modalities. Trial Registration This trial was retrospectively registered on ClinicalTrials.gov (Registration date: 11/19/2021; Registration number: NCT05190055).

We aim to investigate the mechanisms underlying the beneficial effects of exercise rehabilitation (ER) and/or astragaloside (AST) in counteracting amyloid-beta (Aβ) pathology. Aβ oligomers were microinjected into the bilateral ventricles to induce Aβ neuropathology in rats. Neurobehavioral functions were evaluated. Cortical and hippocampal expressions of both BDNF/TrkB and cathepsin D were determined by the western blotting method. The rat primary cultured cortical neurons were incubated with BDNF and/or AST and ANA12 followed by exposure to aggregated Aβ for 24 h. In vivo results showed that ER and/or AST reversed neurobehavioral disorders, downregulation of cortical and hippocampal expression of both BDNF/TrkB and cathepsin D, neural pathology, Aβ accumulation, and altered microglial polarization caused by Aβ. In vitro studies also confirmed that topical application of BDNF and/or AST reversed the Aβ-induced cytotoxicity, apoptosis, mitochondrial distress, and synaptotoxicity and decreased expression of p-TrkB, p-Akt, p-GSK3β, and β-catenin in rat cortical neurons. The beneficial effects of combined ER (or BDNF) and AST therapy in vivo and in vitro were superior to ER (or BDNF) or AST alone. Furthermore, we observed that any gains from ER (or BDNF) and/or AST could be significantly eliminated by ANA-12, a potent BDNF/TrkB antagonist. These results indicate that whereas ER (or BDNF) and/or AST attenuate Aβ pathology by reversing BDNF/TrkB signaling deficits and mitochondrial dysfunction, combining these two potentiates each other’s therapeutic effects. In particular, AST can be an alternative therapy to replace ER.

Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial–mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-β) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-β-induced EMT pathway.

Background: Although whole-body cooling has been reported to improve the ischemic/reperfusion injury in hemorrhagic shock (HS) resuscitation, it is limited by its adverse reactions following therapeutic hypothermia. HS affects the experimental and clinical bowel disorders via activation of the brain-gut axis. It is unknown whether selective brain cooling achieves beneficial effects in HS resuscitation via preserving the integrity of the brain-gut axis. Methods: Male Sprague-Dawley rats were bled to hypovolemic HS and resuscitated with blood transfusion followed by retrograde jugular vein flush (RJVF) with 4 °C or 36 °C normal saline. The mean arterial blood pressure, cerebral blood flow, and brain and core temperature were measured. The integrity of intestinal tight junction proteins and permeability, blood pro-inflammatory cytokines, and multiple organs damage score were determined. Results: Following blood transfusion resuscitation, HS rats displayed gut barrier disruption, increased blood levels of pro-inflammatory cytokines, and peripheral vital organ injuries. Intrajugular-based infusion cooled the brain robustly with a minimal effect on body temperature. This brain cooling significantly reduced the HS resuscitation-induced gut disruption, systemic inflammation, and peripheral vital organ injuries in rats. Conclusion: Resuscitation with selective brain cooling achieves peripheral vital organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.

Amyloid‐beta (Aβ) oligomer is known to contribute to the pathophysiology of age‐related macular degeneration. Herein, we aimed to elucidate the in vivo and in vitro effects of Aβ1‐42 application on retinal morphology in rats. Our in vivo studies revealed that intracerebroventricular administration of Aβ1‐42 oligomer caused dysmorphological changes in both retinal ganglion cells and retinal pigment epithelium. In addition, in vitro studies revealed that ARPE‐19 cells following Aβ1‐42 oligomer application had decreased viability along with apoptosis and decreased expression of the tight junction proteins, increased expression of both phosphor‐AKT and phosphor‐GSK3β and decreased expression of both SIRT1 and β‐catenin. Application of conditioned medium (CM) obtained from mesenchymal stem cells (MSC) protected against Aβ1‐42 oligomer‐induced retinal pathology in both rats and ARPE‐19 cells. In order to explore the potential role of peptides secreted from the MSCs, we applied mass spectrometry to compare the peptidomics profiles of the MSC‐CM. Gene ontology enrichment analysis and String analysis were performed to explore the differentially expressed peptides by predicting the functions of their precursor proteins. Bioinformatics analysis showed that 3‐8 out of 155–163 proteins in the MSC‐CM maybe associated with SIRT1/pAKT/pGSK3β/β‐catenin, tight junction proteins, and apoptosis pathway. In particular, the secretomes information on the MSC‐CM may be helpful for the prevention and treatment of retinal pathology in age‐related macular degeneration.

Abstract Background Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Abstract Background The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). Methods Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. Results The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. Conclusions We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

Pain, the main symptom of osteoarthritis (OA), can lead to functional disability in patients with knee OA. Understanding the association factors related to knee pain is important since preventing OA-induced disabilities can be achieved by modifying these pain-associated issues. Therefore, this study was aimed to investigate the association factors for OA-induced knee pain in Taiwanese patients who received total knee replacements (TKR). In this retrospective study, 357 subjects who had undergone TKR at the Taipei Municipal Wan-Fang Hospital were recruited. The distribution of pain severity among patients with knee OA was evaluated. Demographic data and clinical parameters were analyzed to determine relationships between these variables and the severity of knee OA pain. Of the 357 patients studied, 54% and 33% had moderate and severe knee pain, respectively. Furthermore, a multivariate logistic regression analysis revealed that serum creatinine (>1.5 mg/dL) and an estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m(2)) were significantly associated with severe knee pain in OA patients. A significant correlation between severe knee pain and serum creatinine or eGFR was demonstrated by Pearson correlations. Taken together, the renal insufficiency defined by an elevated serum creatinine or a low eGFR in OA patients who required TKR was associated with severe knee pain. These variables must be considered while treating knee OA pain, especially in those patients with severe pain.

To date, there is no good evidence that intestine epithelial cells (IEC) affected by ischemia/reperfusion (I/R) injury are able to cause cortical neuron injury directly. Additionally, it remains unclear whether the neuronal damage caused by I/R injured IEC can be affected by therapeutic hypothermia (TH, 32 °C). To address these questions, we performed an oxygen–glucose deprivation (OGD) affected IEC-6-primary cortical neuron coculture system under normothermia (37 °C) or TH (32 °C) conditions. It was found that OGD caused hyperpermeability in IEC-6 cell monolayers. OGD-preconditioned IEC-6 cells caused cortical neuronal death (e.g., decreased cell viability), synaptotoxicity, and neuronal apoptosis (evidenced by increased caspase-3 expression and the number of TUNEL-positive cells), necroptosis (evidenced by increased receptor-interacting serine/threonine-protein kinase-1 [RIPK1], RIPK3 and mixed lineage kinase domain-like pseudokinase [MLKL] expression), and pyroptosis (evidenced by an increase in caspase-1, gasdermin D [GSDMD], IL-1β, IL-18, the apoptosis-associated speck-like protein containing a caspase recruitment domain [ASC], and nucleotide oligomerization domain [NOD]-like receptor [NLRP]-1 expression). TH did not affect the intestinal epithelial hyperpermeability but did attenuate OGD-induced neuronal death and synaptotoxicity. We also performed quantitative real-time PCR to quantify the genes encoding 84 exosomal microRNAs in the medium of the control-IEC-6, the control-neuron, the OGD-IEC-6 at 37 °C, the OGD-IEC-6 at 32 °C, the neuron cocultured with OGD-IEC-6 at 37 °C, and the neurons cocultured with OGD-IEC-6 at 32 °C. We found that the control IEC-6 cell s or cortical neurons are able to secrete a basal level of exosomal miRNAs in their medium. OGD significantly up-regulated the basal level of each parameter for IEC-6 cells. As compared to those of the OGD-IEC-6 cells or the control neurons, the OGD-IEC-6 cocultured neurons had significantly higher levels of 19 exosomal miRNAs related to apoptosis, necroptosis, and/or pyroptosis events. Our results identify that I/R injured intestinal epithelium cells can induce cortical neuron death via releasing paracrine mediators such as exosomal miRNAs associated with apoptosis, necroptosis, and/or pyroptosis, which can be counteracted by TH.

To date, cardiac dysfunction after traumatic brain injury (TBI) has not been consistent. In this study, we hypothesized that TBI may play a role in the development of new-onset cardiac dysfunction in healthy experimental rats. Anesthetized healthy male Sprague–Dawley rats were divided into two groups: a sham-operated control group and a TBI group. The brain was injured with 2.4 atm percussion via a fluid percussion injury model. During the 120 min after TBI, we continuously measured brain parameters, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and cardiac parameters, such as heart rate (HR), inter-ventricular septum dimension (IVSD), left ventricular internal dimension diastole (LVIDd), end-diastolic volume (EDV), ejection fraction (EF), fractional shortening (FS), and LV mass diastole (LVd mass) by cardiac echo. On days 1, 3, 7, and 14 after TBI, the brain damage volume was evaluated with triphenyltetrazolium chloride; the physiological parameters of the heart, including HR, IVSd, LVIDd, EDV, EF, FS, and LVd mass, were evaluated with cardiac echo; the morphology of cardiomyocytes was examined by hematoxylin and eosin (HE) and Masson trichrome staining; and the biomarkers of cardiac injury troponin I and B-type natriuretic peptide (BNP) were also examined. Compared to sham-operated controls, the TBI groups had higher ICP, lower CPP, and higher brain neuronal apoptosis and infarction contusion volume. The impact of TBI on heart function showed hyperdynamic response trends in IVSd, LVIDd, EDV, EF, FS, and LVd mass within 30 min after TBI; however, EF and FS exhibited eventual decreasing trends. Simultaneously, the values of the biomarkers troponin I and BNP were within normal limits, and HE and Mass trichrome staining revealed no significant differences between the sham-operated control group and the TBI group. Our results suggest that TBI due to 2.4 atm fluid percussion injury in healthy experimental rats may cause significant damage to the brain and affect the heart function as investigated by cardiac echo but not as investigated by HE and Masson trichrome stainings or troponin I and BNP evaluation.

Injury severity is correlated with poor prognosis after traumatic brain injury (TBI). It is not known whether triglycerides (TGs) or total cholesterol (TC) is good biomarker of increased injury of neuroinflammation and apoptosis in a high fat diet (HFD)-treated rat after TBI episodes. Five-week-old male Sprague–Dawley (SD) rats were fed a HFD for 8 weeks. The anesthetized male SD rats were divided into three sub-groups: sham-operated and TBI with 1.6 atm or with 2.4 atm fluid percussion injury (FPI). Cell infarction volume (triphenyltetrazolium chloride stain), tumor necrosis factor-alpha (TNF-α) expression in the microglia (OX42 marker) and astrocytes (Glial fibrillary acidic protein marker), TNF-α receptor expression in the neurons (TNFR1 and TNFR2 markers), and the extent of neuronal apoptosis (TUNEL marker) were evaluated by immunofluorescence, and the functional outcome was assessed by an inclined plane test. These tests were performed 72 h after TBI. Serum triglyceride and cholesterol levels were measured at 24, 48 and 72 h after TBI. The FPI with 2.4 atm significantly increased body weight loss, infarction volume, neuronal apoptosis and TNF-α expression in the microglia and astrocytes, and it decreased the maximum grasp degree and TNFR1 and TNFR2 expression in neurons at the 3rd day following TBI. The serum TG level was positively correlated with FPI force, infarction volume, Neu-N-TUNEL, GFAP-TNFα, and OX42-TNFα Simultaneously; the serum TG level was negatively correlated with Neu-N-TNFR1 and Neu-N-TNFR2. TG is a good biomarker of increased injury for neuroinflammation and apoptosis at the 3rd day after TBI in HFD rats.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at an increased risk of surgical mortality. We aimed to investigate the factors associated with in-hospital mortality in patients with ESRD who underwent spinal surgery, which remains to be determined. MATERIAL AND METHODS: An age-and sex-matched cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2012. Kaplane-Meier curves were plotted with log-rank test to compare the differences between these 2 groups. The Cox proportional hazard model was used to estimate the hazard ratio of in-hospital mortality adjusted with potential confounding. RESULTS: In total, 4109 participants with pre-existing ESRD and 8218 patients without ESRD were included. The in-hospital mortality in ESRD (10.17%) was greater than without ESRD (1.39%). Spinal surgery patients with preexisting ESRD had a 6.78-fold increase in-hospital mortality risk compared with those without ESRD. Spinal surgery patients with ESRD of any age, male or female, and comorbidities experienced a greater incidence of hospital mortality. In patients with ESRD, operations on spinal cords and spinal canal structures had the greatest hospital mortality (14.87%) compared with spinal fusion (3.46%) or excision or destruction of intervertebral disc (3.01%). Kaplane-Meier survival curves showed that patients with ESRD experienced greater hospital mortality than patients without ESRD in all 3 spinal surgery methods (log rank P < 0.0001). CONCLUSIONS: Spinal surgery patients with ESRD have greater in-hospital mortality than patients without ESRD. Age, sex, history of comorbidities, and types of surgical methods were associated with greater in-hospital mortality among patients with ESRD.

BACKGROUND:High cholesterol has been correlated with a greater risk of cerebrovascular diseases. Whether pre-existing high cholesterol exacerbates traumatic brain injury (TBI), and whether treatment with the cholesterol-lowering agent simvastatin has neuroprotective effects, especially anti-neuroinflammatory effects, after TBI are not well investigated. METHODS:Five-week-old male Sprague-Dawley rats were fed a high-fat diet for 8 weeks to induce hypercholesterolemia. Anesthetized male Sprague-Dawley rats were divided into 5 groups, including the sham-operated control, TBI control, and TBI with simvastatin treatment (4 mg/kg, 10 mg/kg, or 20 mg/kg) groups. Simvastatin was intraperitoneally injected at 0, 24, and 48 hours after TBI. Motor function was measured using an inclined plane. Neuronal apoptosis (maker Neu-N, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling), tumor necrosis factor-α expression in microglia (marker OX42) and astrocytes (marker glial fibrillary acidic protein), and Tumor necrosis factor-alpha receptor (TNFR) 1 and TNFR2 expression in neurons in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the third day after TBI. RESULTS:TBI significantly increased the serum levels of cholesterol. The TBI-induced motor deficit was significantly attenuated by 4, 10, and 20 mg/kg simvastatin therapy on the third day after TBI. TBI-induced neuronal TNFR1 activation and apoptosis, as well as tumor necrosis factor-α expression in astrocytes in the ischemic cortex, were significantly attenuated by simvastatin, particularly when 20 mg/kg was administered. Simultaneously, the serum cholesterol remained high despite simvastatin treatment. CONCLUSIONS:The neuroprotection effects of simvastatin on the pre-existing hypercholesterolemia during TBI in rats may be related to its anti-neuroinflammatory effects but not to its cholesterol-lowing effects.

A high-fat diet (HFD) is correlated with a higher risk of metabolic syndrome. The effect of HFD on neuroinflammation and apoptosis in acute stage after traumatic brain injury (TBI) in rats is not well known. Five-week-old male Sprague-Dawley (SD) rats were fed a HFD or normal diet (ND) for 8 weeks. Anesthetized male SD rats were divided into two subgroups: sham-operated and TBI. Motor function was measured using an inclined plane. The numbers of apoptotic neurons (markers Neu-N, TUNEL, caspase-3), activated astrocytes (marker GFAP) and microglia (marker OX42), and TNF-α expression in microglia and astrocytes in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the 3rd day after TBI. Rats fed a HFD for 8 weeks had higher body weight, serum cholesterol, and triglycerides. TBI-induced motor deficits, neuronal decrease, neuronal apoptosis, astrocyte and microglia activation, and TNF-α expression in microglia and astrocytes in the ischemia cortex were significantly increased in ND and HFD rats compared to sham rats. However, these parameters were not significantly different between the ND and HFD TBI groups, except motor deficit. HFD has no significant effects on neuronal apoptosis or neuroinflammation in acute stage compared with ND for 8 weeks after moderate TBI in experimental rats.