The effect of oxygenation level on cerebral post-traumatic apoptotsis is modulated by the 18-kDa translocator protein (also known as peripheral-type benzodiazepine receptor) in a rat model of cortical contusion.

AIMS: Hyperbaric hyperoxia has been shown to reduce apoptosis in brain injury. As the 18-kDa translocator protein (TSPO), also known as peripheral-type benzodiazepine receptor, is closely associated with the mitochondrial transition pore and because of its role in mitochondrial respiration and apoptosis, we hypothesized that reduction of apoptosis by hyperoxia may involve the TSPO. METHODS: TSPO and transferase-mediated dUTP nick end labelling (TUNEL) immunopositivity was first assessed in cortical contusion, created by dynamic cortical deformation, by immunohistochemistry in rats exposed to normoxia [(dynamic cortical deformation (DCD)], normobaric hyperoxia or hyperbaric hyperoxia [hyperbaric oxygen therapy (HBO)]. In a second step, transmembrane mitochondrial potential (Deltapsi(M)) and caspase 9 activity were assessed in the injured area in comparison with the noninjured hemisphere. Measurements were performed in DCD and HBO groups. A third group receiving both HBO and the TSPO ligand PK11195 was investigated as well. RESULTS: TSPO correlated quantitatively and regionally with TUNEL immunopositivity in the perilesional area. Hyperoxia reduced both the number of TSPO expressing and TUNEL positive cells in the perilesional area, and this effect proved to be pressure dependent. After contusion, we demonstrated a dissipation of Deltapsi(M) in isolated mitochondria and an elevation of caspase 9 activity in tissue homogenates from the contused area, both of which could be substantially reversed by hyperbaric hyperoxia. This protective effect of hyperoxia was reversed by PK11195. CONCLUSIONS: The present findings suggest that the protective effect of hyperoxia may be due to a negative regulation of the proapoptotic function of mitochondrial TSPO, including conservation of the mitochondrial membrane potential.

Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix metalloproteinase-9 in the rat model of traumatic brain injury.

The acute inflammatory response plays an important role in secondary brain damage after traumatic brain injury (TBI). Neutrophils provide the main source of matrix metalloproteinases (MMPs) which also play a deleterious role in TBI. Numerous preclinical studies have suggested that hyperbaric oxygen therapy (HBOT) may by beneficial in various noncerebral and cerebral inflammatory diseases. The goal of this study was to evaluate the effects of HBOT on inflammatory infiltration and the expression of MMPs in correlation with secondary cell death in the rat model of dynamic cortical deformation (DCD). Twenty animals underwent DCD with subsequent HBOT (2.8 ATA, two sessions of 45 min each); 10 animals: DCD and normobaric oxygenation (1 ATA), 10 animals: not treated after DCD. Cell death was evaluated by TUNEL. Neutrophils were revealed by myeloperoxidase staining. Immunohistochemical staining for MMP-2 and -9 and tissue inhibitors of MMP-1 (TIMP-1) and -2 was also performed and the results were quantitatively evaluated by image analysis. In the animals treated by HBOT, a significant decrease in the number of TUNEL-positive cells and neutrophilic inflammatory infiltration was seen in comparison with nontreated animals and those treated by normobaric oxygen. The expression of MMP-9 was also significantly lower in the treated group. Staining for MMP-2 and TIMP-2 did not change significantly. Our results demonstrate that HBOT decreased the extent of secondary cell death and reactive neuroinflammation in the TBI model. The decline of MMP-9 expression after HBOT may also contribute to protection of brain tissue in the perilesional area. Further research should be centred on the evaluation of long-term functional and morphological results of HBOT.

Splenic littoral cell haemangioendothelioma: a new low-grade variant of malignant littoral cell tumour.

AIMS: Littoral cell angioma is a recently described splenic vascular tumour of splenic sinus lining cells. Almost all cases of splenic littoral cell tumours hitherto described were benign. METHODS AND RESULTS: A splenic littoral cell tumour recurred 8 years after splenectomy, with an abdominal mass and multiple liver metastases, resulting in the patient's death. Histologically, the original splenic tumour showed solid areas with small necrotic foci in addition to large areas of typical littoral cell angioma. The recurrent tumours showed increased solid architecture and slightly increased nuclear atypia. The tumours showed an immunohistochemical profile positive for factor VIII, CD31, CD68, cathepsin D, and CD21 and negative for CD34 and CD8, consistent with the immunophenotype of classic littoral cell angioma. Ki67 index in the recurrent tumours was higher than in the primary tumour. CONCLUSIONS: The mildly atypical, but not frankly malignant, histological features as well as the protracted clinical course support definition of the tumour as 'littoral cell haemangioendothelioma'. Low rate of Ki67 staining and diploid DNA histogram with low S-phase fraction of the tumours are in accordance with a low-grade malignancy. Literature review revealed two other cases of littoral cell tumours with disseminated disease that may be other examples of littoral cell haemangioendothelioma. Littoral cell haemangioendothelioma should be distinguished from the overtly malignant splenic angiosarcomas, of which a few may show splenic lining cell differentiation with some immunohistochemical features of littoral cells. Due to difficulties in predicting biological behaviour based on histological features of splenic littoral cell tumours, a long-term follow-up for these patients, especially for those with atypical histology, is recommended.

Primary malignant melanoma of the anterior mediastinum in a child.

Primary malignant melanoma of the mediastinum is extremely rare. We report a case not previously reported of primary malignant melanoma located in the mediastinum in a 11-year-old boy. The tumor could not be completely resected as a result of extensive invasion of the large blood vessels. Histologically, the tumor was heavily pigmented and composed of vague fascicles of spindle cells intermingled with epithelioid cells. Immunohistochemical analysis showed vimentin, S-100 protein, Melan-A, and HMB-45 immunoreactivity in most of the tumor cells. Nearly 50% of the tumor cells were also positive for p53. It is suggested that primary malignant melanoma of the anterior mediastinum may have a histogenetic relationship to the recently described aggregates of nevus cells in the thymus or mediastinal lymph nodes.

Epithelioid angiosarcoma associated with a Dacron vascular graft.

Angiosarcoma developed at the site of a Dacron vascular prosthesis 8 years after an aortobifemoral bypass graft insertion. The tumor was composed of epithelioid cells, which showed positive staining for cytokeratin and expression of the common endothelial markers CD31, CD34, and von Willebrand factor. Ultrastructural examination showed aggregates of large cells with intercellular lumina and focal perinuclear whorls of intermediate filaments. The patient, who had abdominal pain and weight loss, died of disseminated pelvic and abdominal disease 6 months after diagnosis. Sarcomas associated with vascular Dacron grafts and angiosarcomas associated with metal or polymer foreign bodies are rare. Their development is probably analogous to the common experimental development of foreign body-associated sarcomas in rodents. Physicians caring for patients with vascular grafts or metal foreign bodies should be aware of this complication.

Evaluation of muscle capillary basement membrane in inflammatory myopathy. A morphometric ultrastructural study.

The capillary basement membranes from 16 skeletal muscle biopsies from patients with a clinical and histological diagnosis of inflammatory myopathy and from six controls were analysed ultrastructurally and morphometrically. Resin sections from 244 endomysial capillaries were examined by light microscope, and the results were correlated with findings seen in electron micrographs of these capillaries. The ultrastructural morphometric measurements and the statistical analysis showed that the capillary basement membrane was thick and multilaminated in 87% specimens affected by inflammatory myopathy. No thick or multilaminated basement membrane was observed in controls. In inflammatory myopathy the endomysial space next to the capillaries contained an increased amount of collagen fibrils and showed signs of a chronic reparative process. It is suggested that the thick multilaminated basement membrane in inflammatory myopathy represents an advanced stage of vascular regeneration.