Nanoscale mechanics of brain abscess: An atomic force microscopy study.

Mechanical stimuli are a fundamental player in the pathophysiology of the brain influencing its physiological development and contributing to the onset and progression of many diseases. In some pathological states, the involvement of mechanical and physical stimuli might be extremely subtle; in others, it is more evident and particularly relevant. Among the latter pathologies, one of the most serious life-threatening condition is the brain abscess (BA), a focal infection localized in the brain parenchyma, which causes large brain mechanical deformations, giving rise to a wide range of neurological impairments. In this paper, we present the first nano-mechanical characterization of surgically removed human brain abscess tissues by means of atomic force microscopy (AFM) in the spectroscopy mode. Consistently with previous histological findings, we modeled the brain abscess as a multilayered structure, composed of three main layers: the cerebritis layer, the collagen capsule, and the internal inflammatory border. We probed the viscoelastic behavior of each layer separately through the measure of the apparent Young's modulus (E), that gives information about the sample stiffness, and the AFM hysteresis (H), that estimates the contribution of viscous and dissipative forces. Our experimental findings provide a full mechanical characterization of the abscess, showing an average E of (94 ±â€¯5) kPa and H of 0.37 ±â€¯0.01 for the cerebritis layer, an average E = (1.04 ±â€¯0.05) MPa and H = 0.10 ±â€¯0.01 for the collagen capsule and an average E = (9.8 ±â€¯0.4) kPa and H = 0.57 ±â€¯0.01 for the internal border. The results here presented have the potential to contribute to the development of novel surgical instruments dedicated to the treatment of the pathology and to stimulate the implementation of novel constitutive mechanical models for the estimation of brain compression and damage during BA progression.

Nano-mechanical signature of brain tumours.

Glioblastoma (GBM) and meningothelial meningioma (MM) are the most frequent malignant and benign brain lesions, respectively. Mechanical cues play a major role in the progression of both malignancies that is modulated by the occurrence of aberrant physical interactions between neoplastic cells and the extracellular matrix (ECM). Here we investigate the nano-mechanical properties of human GBM and MM tissues by atomic force microscopy. Our measures unveil the mechanical fingerprint of the main hallmark features of both lesions, such as necrosis in GBM and dural infiltration in MM. These findings have the potential to positively impact on the development of novel AFM-based diagnostic methods to assess the tumour grade. Most importantly, they provide a quantitative description of the tumour-induced mechanical modifications in the brain ECM, thus being of potential help in the search for novel ECM targets for brain tumours and especially for GBM that, despite years of intense research, has still very limited therapeutic options.

Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.

AIMS AND BACKGROUND: Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor. PATIENTS AND METHODS: Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30). RESULTS: Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years). CONCLUSIONS: Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.