Delayed CO2 postconditioning promotes neurological recovery after cryogenic traumatic brain injury by downregulating IRF7 expression.

AIMS: Few treatments are available in the subacute phase of traumatic brain injury (TBI) except rehabilitation training. We previously reported that transient CO2 inhalation applied within minutes after reperfusion has neuroprotective effects against cerebral ischemia/reperfusion injury. In this study, it was hypothesized that delayed CO2 postconditioning (DCPC) starting at the subacute phase may promote neurological recovery of TBI. METHODS: Using a cryogenic TBI (cTBI) model, mice received DCPC daily by inhaling 5%/10%/20% CO2 for various time-courses (one/two/three cycles of 10-min inhalation/10-min break) at Days 3-7, 3-14 or 7-18 after cTBI. Beam walking and gait tests were used to assess the effect of DCPC. Lesion size, expression of GAP-43 and synaptophysin, amoeboid microglia number and glia scar area were detected. Transcriptome and recombinant interferon regulatory factor 7 (Irf7) adeno-associated virus were applied to investigate the molecular mechanisms. RESULTS: DCPC significantly promoted recovery of motor function in a concentration and time-course dependent manner with a wide therapeutic time window of at least 7 days after cTBI. The beneficial effects of DCPC were blocked by intracerebroventricular injection of NaHCO3 . DCPC also increased puncta density of GAP-43 and synaptophysin, and reduced amoeboid microglia number and glial scar formation in the cortex surrounding the lesion. Transcriptome analysis showed many inflammation-related genes and pathways were altered by DCPC, and Irf7 was a hub gene, while overexpression of IRF7 blocked the motor function improvement of DCPC. CONCLUSIONS: We first showed that DCPC promoted functional recovery and brain tissue repair, which opens a new therapeutic time window of postconditioning for TBI. Inhibition of IRF7 is a key molecular mechanism for the beneficial effects of DCPC, and IRF7 may be a potential therapeutic target for rehabilitation after TBI.

The immunomodulatory effects of ethosuximide and sodium butyrate on experimentally induced fibromyalgia: The interaction between IL-4, synaptophysin, and TGF-ß1/NF-κB signaling.

BACKGROUND AND AIMS: Fibromyalgia is a widespread chronic pain syndrome associated with several comorbid conditions that affect the quality of patients' life. Its pathogenesis is complex, and the treatment strategies are limited by partial efficacy and potential adverse effects. So, our aim was to investigate the possible ameliorative effects of ethosuximide and sodium butyrate on fibromyalgia and compare their effects to pregabalin. MATERIALS AND METHODS: In a mouse model of reserpine induced fibromyalgia, the effect of ethosuximide, sodium butyrate, and pregabalin was investigated. Evaluation of mechanical allodynia, cold hypersensitivity, anxiety, cognitive impairment, and depression was performed. Also, the brain and spinal cord tissue serotonin, dopamine and glutamate in addition to the serum levels of interleukin (IL)-4 and transforming growth factor beta 1 (TGF-ß1) were assayed. Moreover, the expression of nuclear factor kappa B (NF-κB) synaptophysin was immunoassayed in the hippocampal tissues. KEY FINDINGS: Ethosuximide and sodium butyrate restored the behavioral tests to the normal values except for the antidepressant effect which was evident only with ethosuximide. Both drugs elevated the levels of the anti-inflammatory cytokines IL-4 and TGF-ß1, reduced the hippocampal NF-κB, and increased synaptophysin expression with superiority of sodium butyrate. Ethosuximide reduced only spinal cord and brain glutamate while improved brain dopamine while sodium butyrate elevated spinal cord dopamine and serotonin with no effect on glutamate. Also, sodium butyrate elevated brain serotonin and reduced glutamate with no effect on brain dopamine. SIGNIFICANCE: Each of sodium butyrate and ethosuximide would serve as a promising therapeutic modality for management of fibromyalgia and its comorbid conditions.

Primary extraskeletal Ewing's sarcoma presenting as an axillary mass: A case report and review of the literature.

Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor predominantly observed in adolescents and young adults, and is characterized by aggressive behavior. So far, only two cases of primary axillary soft tissue EES have been reported in the literature. One of them was a 29-year-old female patient who presented with a lump in her left axilla. Upon examination, an irregular, painless mass, measuring 5 cm × 5 cm × 3 cm, was noted in the left axilla. A histopathological examination of the mass revealed small, round, blue cells with scant cytoplasm, round nuclei, numerous mitosis, and necrosis. An immunohistochemistry (IHC) examination was positive for CD99 and negative for ER, PR, Her2neu, CK7, CK5/6, CD56, CD45, CK-pan, CKHMW, P63, desmin, S100, TdT, vimentin, myogenin, synaptophysin, and chromogranin A. The patient was diagnosed with primary axillary soft tissue EES and was started on neoadjuvant chemotherapy. Twelve months later, she is clinically free from the disease.

Immunophenotypic features of immaturity of neural elements in ovarian teratoma.

Neural components in mature teratomas are common and the general assumption is that they are quite similar to those in the mature central nervous system (CNS). We investigated 44 ovarian teratomas by immunohistochemistry to determine cellular and structural immaturity of neural elements. Most teratomas contained cells differentiating into astrocytes positive for nestin, a neural stem cell marker. These nestin-positive astrocytes generally co-expressed glial fibrillary acidic protein-delta, an immature astrocyte marker. Olig2-positive cells were randomly scattered. Areas comprising cells that differentiated into neurons were positive for NeuN and synaptophysin. The border between white and gray matter was ill-defined and more NeuN-positive cells were distributed in areas that were positive for myelin basic protein, indicating that the distribution of neurons and glial cells was disturbed. Peripheral nerve bundles positive for Schwann/2E, an antigen specific for myelinating Schwann cells, were mixed within CNS-like tissues. These results show that apparently mature teratomas are not in fact mature, at least in terms of neural elements, as they harbor immature cells and structural abnormalities. The neural elements of surgically resected teratomas might represent a premature state of the human CNS, and thus be potentially useful for studies of developmental neurobiology as well as gliomagenesis.

Clinicopathological features and prognosis of gastroenteropancreatic neuroendocrine tumors: analysis from a single-institution.

BACKGROUND: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. METHOD: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. RESULTS: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (χ2=32.825, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. CONCLUSIONS: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.

Primitive neuroectodermal tumor of adrenal: clinical presentation and outcomes.

Primitive neuroectodermal tumor (PNET) of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm) on computed tomography (CT) was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE). This is the first report of adrenal peripheral PNET (pPNET) from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.