Traumatic brain injury is a major source of global disability and mortality. Preclinical TBI models are a crucial component of therapeutic investigation. We report a tunable, monitored model of murine non-surgical, diffuse closed-head injury—modCHIMERA—characterized by impact as well as linear and rotational acceleration. modCHIMERA is based on the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) platform. We tested this model at 2 energy levels: 1.7 and 2.1 Joules—substantially higher than previously reported for this system. Kinematic analysis demonstrated linear acceleration exceeding injury thresholds in humans, although outcome metrics tracked impact energy more closely than kinematic parameters. Acute severity metrics were consistent with a complicated-mild or moderate TBI, a clinical population characterized by high morbidity but potentially reversible pathology. Axonal injury was multifocal and bilateral, neuronal death was detected in the hippocampus, and microglial neuroinflammation was prominent. Acute functional analysis revealed prolonged post-injury unconsciousness, and decreased spontaneous behavior and stimulated neurological scores. Neurobehavioral deficits were demonstrated in spatial learning/memory and socialization at 1-month. The overall injury profile of modCHIMERA corresponds with the range responsible for a substantial portion of TBI-related disability in humans. modCHIMERA should provide a reliable platform for efficient analysis of TBI pathophysiology and testing of treatment modalities.
Circulating biomarker for malignant gliomas could improve both differential diagnosis and clinical management of brain tumor patients. Among all gliomas, glioblastoma (GBM) is considered the most hypervascularized tumor with activation of multiple proangiogenic signaling pathways that enhance tumor growth. To investigate whether preoperative antigen plasma level of von Willebrand Factor (VWF:Ag) might be possible marker for GBM onset, progression, and prognosis, we retrospectively examined 57 patients with histological diagnosis for GBM and 23 meningiomas (MNGs), benign intracranial expansive lesions, enrolled as controls. Blood samples were collected from all the patients before tumor resection. Plasma von Willebrand Factor (VWF):Ag levels were determined by using a latex particle‐enhanced immunoturbidimetric assay. The median levels of vWF:Ag were significantly higher in GBMs than in meningiomas (MNGs) (183 vs. 133 IU/dL, P = 0.01). The cumulative 1‐year survival was significantly shorter in patients with VWF:Ag levels >200 IU/dL than in those with levels <200 IU/dL and increased VWF levels were associated with a threefold higher risk of death in GBM patients. Our data suggest that VWF:Ag could be a circulating biomarker of disease malignancy, that could be considered, in association with other genetic and epigenetic factors, currently available in the GBM management. Future studies should investigate whether plasma VWF:Ag levels could also be used to monitor therapeutic effects and whether it may have a prognostic value.
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