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Excessive beta activity has been shown in local field potential recordings from the cortico-basal ganglia loop of Parkinson's disease patients and in its various animal models. Recent evidence suggests that enhanced beta oscillations may play a central role in the pathophysiology of the disorder and that beta activity may be directly linked to the motor impairment. However, the temporal evolution of exaggerated beta oscillations during the ongoing dopaminergic neurodegeneration and its relation to the motor impairment and histological changes are still unknown. We investigated motor behavioral, in-vivo electrophysiological (subthalamic nucleus, motor cortex) and histological changes (striatum, substantia nigra compacta) 2, 5, 10 and 20-30 days after a 6-hydroxydopamine injection into the medial forebrain bundle in Wistar rats. We found strong correlations between subthalamic beta power and motor impairment. No correlation was found for beta power in the primary motor cortex. Only subthalamic but not cortical beta power was strongly correlated with the histological markers of the dopaminergic neurodegeneration. Significantly increased subthalamic beta oscillations could be detected before this increase was found in primary motor cortex. At the latest observation time point, a significantly higher percentage of long beta bursts was found. Our study is the first to show a strong relation between subthalamic beta power and the dopaminergic neurodegeneration. Thus, we provide additional evidence for an important pathophysiological role of subthalamic beta oscillations and prolonged beta bursts in Parkinson's disease.

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The antiangiogenic splice variant VEGF-A165b is downregulated in a variety of cancer entities, but little is known so far about circulating plasma levels. The present analysis addresses this question and examines circulating VEGF-A/VEGF-A165b levels in a collective of female high-risk breast cancer patients over the course of treatment. Within the SUCCES-A trial 205 patients were recruited after having received primary breast surgery. Using ELISA VEGF-A/VEGF-A165b concentrations were determined and correlated to clinical characteristics (1) before adjuvant chemotherapy, (2) four weeks and (3) two years after therapy and compared to healthy controls (n = 107). VEGF 165b levels were significantly elevated after completion of chemotherapy. Within the breast cancer cohort, VEGF-A165b levels increased two years after completion of chemotherapy. VEGF-A plasma concentrations were significantly elevated in the breast cancer cohort at all examined time points and decreased after treatment. VEGF-A levels two years after chemotherapy correlated with increased cancer related mortality, no such correlation could be found between VEGF-A165b and the examined clinical characteristics. Compared to controls, VEGF-A/ VEGF-A165b ratios were decreased in patients before and after chemotherapy. Our data suggests that circulating VEGF-A165b is significantly reduced in women with primary breast cancer at time of diagnosis; furthermore, levels change during adjuvant treatment. Already in the 19th century, the great pathologist Rudolf Virchow described the abundant vascularization found in many tumors 1. However, almost another century needed to pass until Senger discovered in 1983 a protein which led to a strong increase in the permeability of abdominal vasculature which he therefore named "vascular permeability factor" 2. In 1989 Ferrara and colleagues found a heparin binding growth factor that specifically activated vascular endothelial cells and coined the term vascular endothelial growth factor VEGF 3. Now we know that VEGF is not only one protein, but rather a family of growth factors with a similar protein structure but different abilities. Seven different human glycoproteins termed VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental like growth factor (PlGF) have been identified so far 4. VEGF-A is a family of different isoforms (VEGF-A121, VEGF-A165, VEGF-A183, VEGF-A189, VEGF-A206 and VEGF-A165b) with different functions and sizes. The coding gen for it lies on chromosome 6p21.3 5 and consists of eight exons and seven introns 6. Alternative splicing at exon six and seven as well as at the proximal end of exon 8a leads to a variety of proangiogenic isoforms of VEGF. In 2002 Bates et al. 7 were the first to describe a new splice variant that differed from the known ones in its biologic function. This splice variant named VEGF-A165b deviates from VEGF-A in six amino acids at the carboxy terminal 3′ end changing the exonic structure from CDKPRR to SLTRKD and from an angiogenic to

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