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Brain trauma causes the onset of an inflammatory process within the dural border cell layer; high levels of inflammatory cytokines were significantly correlated with recurrence and layering CSDH. A prolonged postoperative antiinflammatory medicine given as prophylaxis may help prevent the recurrence of a CSDH.

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders.

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BackgroundAdaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM). The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs), hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype.MethodsFrom each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB). GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior.ResultsA panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3) were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry) were excluded. Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas), less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues. Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells. Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells.ConclusionsIn human solid glioblastoma we have observed a coordinated overexpression of a panel of pro-inflammatory genes as compared to host normal tissue. We have also evidenced a similar pattern of overexpressed genes in GBM-SCs after hypoxic treatment, showing also a gain of invasive and migratory function that was lost when these stem cells differentiated. We suggest that, as has been previously described for prostatic and mammary carcinoma, in human glioblastoma acquisition of a proinflammatory phenotype may be relevant for malignant progression.

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The authors report their 27-year experience regarding 35 cases of supratentorial brain metastasis from sarcoma treated in a single institution: these included ten osteosarcomas, seven leiomyosarcomas, five Ewing sarcomas, four malignant fibrous histiocytomas, three alveolar soft-part sarcomas (ASPS), two rhabdomyosarcomas, one liposarcoma, and three unclassified sarcomas. The first 15 cases of the series have already been described in a previous publication. Median survival after craniotomy was 9.8 months (range: 4-24). In patients with preoperative Karnofsky performance score (KPS) > 60 it was 12.8 months (range: 6.5-24 months) versus 5.4 months for those patients with a KPS < or = 60 (P = 0.01). Eight patients had more than one lesion, six of which were treated in the last ten years. Of the three patients with ASPS, the first two were alive at 15 and 20 months (before being lost to follow-up) whereas the third patient is alive at 24 month follow-up. The authors conclude that surgery is more effective in treating selected patients with sarcoma metastatic to the brain, and that patients with metastasis from ASPS have good prognosis when submitted to surgical treatment. The complete removal of all brain metastases "en bloc" and a KPS > 60 are associated with the best prognosis. Finally, it seems that surgical indications for multiple brain metastases from sarcoma have increased during the last ten years.

We found 128 cases of extra CNS metastases in the English literature. The main features of the patients of the previous reports and of those of the present series were analyzed. The main modalities of glioblastoma multiforme spread, the few theories about the rarity of metastasis, and the probable biological, histological and immunogenetic mechanisms involved in the pathogenesis are described. Although several studies have reported a poor outcome in elderly patients, they affirm that the treatment of those with a Karnofsky performance status >60 should be just as aggressive as in younger patients. This allows them to obtain a longer survival time and to also treat metastases, which are uncommon particularly in the elderly.