Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months--on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test--were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present.

Bevacizumab as salvage therapy for progressive brain stem gliomas.

OBJECTIVE: There is no standard of care for patients with progredient brain stem gliomas. Therefore, we report about clinical, radiological and metabolic response to anti-angiogenic treatment with bevacizumab in a series of 3 patients with gliomas involving the brain stem. PATIENTS AND METHODS: Three patients with histologically confirmed gliomas involving the brain stem were treated with bevacizumab for tumor progression. The clinical data, histopathological findings as well as MRI and PET follow up examinations during bevacizumab therapy were retrospectively analyzed. RESULTS: The histopathological diagnosis revealed an anaplastic astrocytoma WHO grade III in two patients and an astrocytoma WHO grade II in 1 patients with clinical and neuroradiological signs of malignization. One patient is still progression-free 97 weeks after initiation of bevacizumab therapy. Mean progression-free survival and overall survival for the other two patients after initiation of bevacizumab therapy was 34.5 weeks and 43.5 weeks. During bevacizumab therapy mean KPS improved from 60 to 80 and mean dosage of daily dexamathasone was reduced from 7.3 mg to 1.3 mg. MRI showed a decrease of T2 weighted hyperintense lesions in all patients and a decrease of contrast enhancement in two patients. (18)F-FET-PET showed a decrease of tracer uptake in all cases (mean maximum decrease: 25%). CONCLUSION: In this series treatment of progressive gliomas involving the brain stem with bevacizumab resulted in an improved clinical condition of the patients as well as a reduction of the T2 weighted lesions and reduced amino acid uptake in the tumor area. It therefore may represent a therapeutic salvage option for this type of tumor.

PET and SPECT for radiation treatment planning.

Positron emission tomography (PET) and single photon computed emission tomography (SPECT) have been evaluated in several studies for radiation treatment planning in patients with primary brain tumors. PET with the glucose analogue fluorodeoxyglucose has been found to be of limited use for radiation treatment planning because the high physiologic glucose use of normal gray matter makes delineation of tumors challenging. In contrast, there is considerable evidence that PET or SPECT with radiolabeled amino acid or amino acid analogues provides valuable information for the delineation of gliomas. Increased amino acid uptake has been found to be a more specific marker for viable tumor tissue than signal abnormalities on MRI. In addition, increased amino acid uptake is frequently observed in tumor areas that have not caused a disruption of the blood brain barrier. Therefore, PET and SPECT with radiolabeled amino acids provide a unique opportunity to visualize the infiltrative growth of gliomas and use this information for radiation treatment planning.