Attenuation of Heat-Induced Hypothalamic Ischemia, Inflammation, and Damage by Hyperbaric Oxygen in Rats.

The present study was attempted to assess the mechanisms underlying the beneficial effects of hyperbaric oxygen (HBO2; 100% O2 at 253 kpa) in treating experimental heatstroke. Anesthetized rats were divided into five major groups: normothermic control (NC) rats treated with normobaric air (NBA; 21% O2 at 101 kpa; NC + NBA); NC rats treated with HBO2 (NC + HBO2); heatstroke (HS) rats treated with NBA (HS + NBA); HS rats treated with hyperbaric air (HBA; 21% at 253 kpa; HS + HBA); and HS rats treated with HBO2 (HS + HBO2). HS groups were exposed to heat (43°C) for exactly 68 min and then allowed to recover at 26°C. HBA or HBO2 was adopted 68 or 78 min after the start of heat exposure. Survival time values for (HS + NBA) rats, (HS + HBA) rats at 68 min, (HS + HBA) rats at 78 min, (HS + HBO2) rats at 68 min, and (HS + HBO2) rats at 78 min were found to be 90 ± 3, 133 ± 12, 109 ± 9, 240 ± 18, and 170 ± 15 min, respectively. Resuscitation with HBA or HBO2 at 68 min was superior to those treated at 78 min in prolonging the survival time values. All (HS + NBA) animals displayed hyperthermia, hypotension, and increased cellular levels of ischemia, oxidative stress and damage markers, pro-inflammatory cytokines, and an indicator of polymorphonuclear cell accumulation in their hypothalamus as compared to those of NCs. Heat-induced hyperthermia was not affected by HBA or HBO2 treatment. However, heat-induced hypotension and hypothalamic ischemia, oxidative stress, neuronal damage, and inflammation were all significantly reduced by HBA or HBO2 therapy. Compared to those of HBA therapy, HBO2 therapy had a significantly higher beneficial effect in treating heatstroke. Our results suggested that HBO2 improved heatstroke outcomes, in part, by restoring normal hypothalamic function. Delaying the onset of HBO2 therapy reduced the therapeutic efficiency.

Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration.

BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration is related to numerous risk factors, including obesity. Leptin, one of the commonly measured adipokines, is proven to play an important role in the pathogenesis of IVD degeneration. In the context of IVD degeneration, matrix metalloproteinase-1 (MMP-1), which is upregulated and activated by leptin, is the most abundant catabolic enzyme. It remains unclear which of the factors mentioned above is most strongly associated with IVD degeneration. PURPOSE: To investigate the influence of MMP-1 in IVD degeneration, we determined the strength of different predictors, including age, sex, magnetic resonance imaging (MRI), Modic changes (MCs), body mass index (BMI), leptin, and MMP-1. This was achieved by assessing the correlation among these factors and histologic degeneration score (HDS). STUDY DESIGN: This study included 89 patients undergoing cervical discectomy for disc herniation, 93 who underwent lumbar discectomy, and 90 control subjects. Herniated disc tissue and plasma were used after the study was approved by the Human Ethics Review Committee at the authors' institution. METHODS: Hematoxylin and eosin (H&E), Alcian blue-PAS and immunohistochemical (IHC) staining were performed to measure the expression levels of leptin and MMP-1. Circulating plasma levels of leptin and MMP-1 were measured using an enzyme-linked immunosorbent assay. To assess the correlation with HDS, measurements of age, sex, BMI, MRI scale, MCs scale, leptin/MMP-1 plasma concentration, and leptin/MMP-1 IHC expression were analyzed. RESULTS: Patients with cervical or lumbar discectomy had significantly higher BMI than controls. Significantly more men than women were involved in the lumbar patients as compared with the cervical patients and the control subjects. After adjustment for age and sex, plasma leptin and leptin IHC score correlated significantly with BMI in patients with cervical or lumbar discectomy. Age, sex, MRI scale, MCs scale, and leptin/MMP-1 plasma concentration were not positively correlated with HDS. HDS was significantly associated with BMI, leptin IHC score, and MMP-1 IHC score. After a stepwise-multiple linear regression analysis to evaluate the strength of the correlations between HDS and various factors, only the MMP-1 IHC score demonstrated an independent association with HDS in patients with degeneration of the cervical or lumbar disc. CONCLUSIONS: MMP-1 IHC score is an independent predictor of the severity of cervical or lumbar IVD degeneration. CLINICAL SIGNIFICANCE: MMP-1 IHC score may be used as an indicator of IVD degeneration.

Congenital exercise ability ameliorates muscle atrophy but not spinal cord recovery in spinal cord injury mouse model.

Spinal cord injury (SCI) can cause loss of mobility in the limbs, and no drugs, surgical procedures, or rehabilitation strategies provide a complete cure. Exercise capacity is thought to be associated with the causes of many diseases. However, no studies to date have assessed whether congenital exercise ability is related to the recovery of spinal cord injury. High congenital exercise ability (HE) and low congenital exercise ability (LE) mice were artificially bred from the same founder ICR mice. The HE and LE groups still exhibited differences in exercise ability after 13 generations of breeding. Histological staining and immunohistochemistry staining indicated no significant differences between the HE and LE groups on recovery of the spinal cord. In contrast, after SCI, the HE group exhibited better mobility in gait analysis and longer endurance times in the exhaustive swimming test than the LE group. In addition, after SCI, the HE group also exhibited less atrophy than the LE group, and no inflammatory cells appeared. In conclusion, we found that high congenital exercise ability may reduce the rate of muscle atrophy. This result can be applied to sports science and rehabilitation science as a reference for preventive medicine research.

The Development and Applications of a Dual Optical Imaging System for Studying Glioma Stem Cells.

Glioblastoma multiforme represents one of the deadliest brain tumor types, manifested by a high rate of recurrence and poor prognosis. The presence of glioma stem cells (GSCs) can repopulate the tumor posttreatment and resist therapeutics. A better understanding of GSC biology is essential for developing more effective interventions. We established a CD133 promoter-driven dual reporter, expressing green fluorescent protein (GFP) and firefly luciferase (CD133-LG), capable for in vitro and in vivo imaging of CD133+ GSCs. We first demonstrated the reporter enabled in vitro analyses of GSCs. DBTRG-05MG (Denver Brain Tumor Research Group 05) carrying CD133-LG (DBTRG-05MG-CD133-LG) system reported increased GFP/luciferase activities in neurospheres. Additionally, we identified and isolated CD133+/GFP+ cells with increased tumorigenic properties, stemness markers, Notch1, ß-catenin, and Bruton's tyrosine kinase (Btk). Furthermore, prolonged temozolomide (TMZ) treatment enriched GSCs (reflected by increased percentage of CD133+ cells). Subsequently, Btk inhibitor, ibrutinib, suppressed GSC generation and stemness markers. Finally, we demonstrated real-time evaluation of anti-GSC function of ibrutinib in vivo with TMZ-enriched GSCs. Tumorigenesis was noninvasively monitored by bioluminescence imaging and mice that received ibrutinib showed a significantly lower tumor burden, indicating ibrutinib as a potential GSC inhibitor. In conclusion, we established a dual optical imaging system which enables the identification of CD133+ GSCs and screening for anti-GSC drugs.

Increased Risk of Dementia in Patients with Antidepressants: A Meta-Analysis of Observational Studies.

Antidepressants are the most commonly and widely used medication for its effectiveness in the treatment of anxiety and depression. A few epidemiological studies have documented that antidepressant is associated with increased risk of dementia so far. Here, our aim is to assess the association between antidepressant use and risk of dementia in elderly patients. We searched articles through MEDLINE, EMBASE, Google, and Google Scholar from inception to December 1, 2017, that reported on the association between antidepressant use and dementia risk. Data were collected from each study independently, and study duplication was checked by at least three senior researchers based on a standardized protocol. Summary relative risk (RR) with 95% CI was calculated by using a random-effects model. We selected 9 out of 754 unique abstracts for full-text review using our predetermined selection criteria, and 5 out of these 9 studies, comprising 53,955 participants, met all of our inclusion criteria. The overall pooled RR of dementia was 1.75 (95% CI: 1.033-2.964) for SSRIs whereas the overall pooled RR of dementia was 2.131 (95% CI: 1.427-3.184) for tricyclic use. Also, MAOIs showed a high rate of increase with significant heterogeneity. Our findings indicate that antidepressant use is significantly associated with an increased risk of developing dementia. Therefore, we suggest physicians to carefully prescribe antidepressants, especially in elder patients. Additionally, treatment should be stopped if any symptoms related to dementia are to be noticed.

Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2cm(3) to 21.9cm(3). Regarding the dose homogeneity index (HIICRU) and conformity index (CIICRU) were without significant difference between techniques statistically. However, the average CIICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V4Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V2Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better (p < 0.05) than either DCA or IMRS plans, at 9.2 ± 7% and 8.2 ± 6%, respectively. Owing to the multiple arc or beam planning designs of IMRS and VMAT, both of these techniques required higher MU delivery than DCA, with the averages being twice as high (p < 0.05). If linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem.

Lumbar Intradural Ganglion Cyst.

BACKGROUND: Lumbar intraspinal ganglion cysts are a rare cause of lumbar radiculopathy. These cysts are often extradural and next to facet joints. Sometimes they are related to ligamentum flavum or posterior longitudinal ligament. To our knowledge, lumbar intradural ganglion cyst has not been reported to date. CASE DESCRIPTION: We report a case of a fifth lumbar intradural ganglion cyst in an elderly patient presenting with insidious onset of left-sided lower limb pain. Magnetic resonance imaging of the lumbar spine revealed a left-sided ventrolateral intraspinal cystic lesion abutting on the fifth lumbar vertebral body with ring enhancement of the cyst wall. During surgery, no lesion was found related to the facet joint or in the epidural space. Instead, a dura-based septated ganglion cyst was noted intradurally. The patient's discomfort was completely relieved postoperatively. Follow-up magnetic resonance imaging showed complete removal of the cyst. CONCLUSIONS: A lumbar intradural dura-based ganglion cyst in an elderly patient led to compressive radiculopathy. Total removal of the cyst was achieved, and the patient's discomfort was completely relieved after surgery. The origin and pathogenesis of the lumbar intradural ganglion cyst are still unknown. Surgical extirpation is regarded as the treatment of choice.

Low-intensity pulsed ultrasound stimulates matrix metabolism of human annulus fibrosus cells mediated by transforming growth factor ß1 and extracellular signal-regulated kinase pathway.

PURPOSE: There are limited strategies to restore the damaged annulus fibrosus (AF) of the intervertebral disc. Low-intensity pulsed ultrasound (LIPUS) has positive effects on the proliferation of several types of cells and the repair of damage tissue in vivo. However, scientific evidence of therapeutic effects of LIPUS on AF cells remains limited. The purpose of this study is to evaluate the feasibility of applying LIPUS to the repair of the AF. MATERIALS AND METHODS: We used an in vitro model of human AF cells subjected to LIPUS stimulation to examine its effects on cell proliferation and matrix metabolism. Cell viability, synthesis of collagen and glycosaminoglycan (GAG), expression of matrix metalloproteinases (MMPs) and transforming growth factor ß1 and pathways involving mitogen-activated protein kinases (MAPKs) were investigated. RESULTS: LIPUS significantly enhanced proliferation of AF cells after 5 days of treatment. LIPUS with an intensity of 0.5 W/cm(2) increased the collagen and GAG synthesis and decreased the expressions of MMP-1 and -3 of human AF cells. Real-time polymerase chain reactions and western blotting analysis revealed that LIPUS could increase transforming growth factor ß1 (TGF-ß1) and activate extracellular signal-regulated kinase (ERK) pathway. In addition, TGF-ß receptor kinase inhibitor could suppress the ultrasound-induced alterations in cell viability and matrix metabolism. CONCLUSIONS: The findings suggested that LIPUS could be useful as a physical stimulation of cell metabolism for the repair of the AF.

Laparoendoscopic single-site retroperitoneal lumbar sympathectomy: initial report.

BACKGROUND: Retroperitoneoscopic lumbar sympathectomy is a safe and effective treatment for plantar hyperhidrosis. OBJECTIVE: To evaluate the safety and feasibility of laparoendoscopic single-site retroperitoneal lumbar sympathectomy in plantar hyperhidrosis. METHODS: Bilateral laparoendoscopic single-site retroperitoneal lumbar sympathectomy was performed in a 27-year-old man who suffered from excessive sweating from the soles of the feet. A homemade single port was created with an Alexis wound retractor through a 2.5-cm incision at the tip of the 12th rib. With conventional 5-mm laparoscopy and instruments, retroperitoneal lumbar sympathectomy was performed. RESULTS: The procedure was completed successfully without any complications and with minimal blood loss. The operative time was 110 and 80 minutes for the procedure on the left and right sides. The perioperative course and postoperative course were uneventful. The patient had anhidrosis of both feet after surgery with Hyperhidrosis Disease Severity Scale score of 1 at the 1-month follow-up. CONCLUSION: Laparoendoscopic single-site retroperitoneal lumbar sympathectomy is a safe and feasible procedure according to our initial experience.

Reduction of ischemic and oxidative damage to the hypothalamus by hyperbaric oxygen in heatstroke mice.

The aims of the present paper were to ascertain whether the heat-induced ischemia and oxidative damage to the hypothalamus and lethality in mice could be ameliorated by hyperbaric oxygen therapy. When normobaric air-treated mice underwent heat treatment, the fractional survival and core temperature at 4 hours after heat stress were found to be 0 of 12 and 34 degrees C +/- 0.3 degrees C, respectively. In hyperbaric oxygen-treated mice, when exposed to the same treatment, both fractional survival and core temperature values were significantly increased to new values of 12/12 and 37.3 degrees C +/- 0.3 degrees C, respectively. Compared to normobaric air-treated heatstroke mice, hyperbaric oxygen-treated mice displayed lower hypothalamic values of cellular ischemia and damage markers, prooxidant enzymes, proinflammatory cytokines, inducible nitric oxide synthase-dependent nitric oxide, and neuronal damage score. The data indicate that hyperbaric oxygen may improve outcomes of heatstroke by normalization of hypothalamic and thermoregulatory function in mice.

Attenuating experimental spinal cord injury by hyperbaric oxygen: stimulating production of vasculoendothelial and glial cell line-derived neurotrophic growth factors and interleukin-10.

The present study was carried out to further examine the mechanisms underlying the beneficial effects of hyperbaric oxygen (HBO(2)) on experimental spinal cord injury (SCI). Rats were divided into three major groups: (1) sham operation (laminectomy only); (2) laminectomy + SCI + normobaric air (NBA; 21% oxygen at 1 ATA); and (3) laminectomy + SCI + HBO(2) (100% oxygen at 2.5 ATA for 2 h). Spinal cord injury was induced by compressing the spinal cord for 1 min with an aneurysm clip calibrated to a closing pressure of 55 g. HBO(2) therapy was begun immediately after SCI. Behavioral tests of hindlimb motor function as measured by the Basso, Beattie, and Bresnahan (BBB) locomotor scale was conducted on days 1-7 post-SCI. The triphenyltetrazolium chloride staining assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay were also conducted after SCI to evaluate spinal cord infarction and apoptosis, respectively. Cells positive for glial cell line-derived neurotrophic nerve growth factor (GDNF) and vascular endothelial growth factor (VEGF) and cytokines in the injured spinal cord were assayed by immunofluorescence and commercial kits, respectively. It was found that HBO(2) therapy significantly attenuated SCI-induced hindlimb dysfunction, and spinal cord infarction and apoptosis, as well as overproduction of spinal cord interleukin-1beta and tumor necrosis factor-alpha. In contrast, the numbers of both GDNF-positive and VEGF-positive cells and production of spinal cord interleukin-10 after SCI were all significantly increased by HBO(2). These data suggest that HBO(2) may attenuate experimental SCI by stimulating production of GDNF, VEGF, and interleukin-10.