TY  - JOUR
A1  - Pötter-Nerger, Monika
A1  - Reese, Rene
A1  - Steigerwald, Frank
A1  - Heiden, Jan Arne
A1  - Herzog, Jan
A1  - Moll, Christian K. E.
A1  - Hamel, Wolfgang
A1  - Ramirez-Pasos, Uri
A1  - Falk, Daniela
A1  - Mehdorn, Maximilian
A1  - Gerloff, Christian
A1  - Deuschl, Günther
A1  - Volkmann, Jens
T1  - Movement-Related Activity of Human Subthalamic Neurons during a Reach-to-Grasp Task
JF  - Frontiers in Human Neuroscience
N2  - The aim of the study was to record movement-related single unit activity (SUA) in the human subthalamic nucleus (STN) during a standardized motor task of the upper limb. We performed microrecordings from the motor region of the human STN and registered kinematic data in 12 patients with Parkinson’s disease (PD) undergoing deep brain stimulation surgery (seven women, mean age 62.0 ± 4.7 years) while they intraoperatively performed visually cued reach-to-grasp movements using a grip device. SUA was analyzed offline in relation to different aspects of the movement (attention, start of the movement, movement velocity, button press) in terms of firing frequency, firing pattern, and oscillation. During the reach-to-grasp movement, 75/114 isolated subthalamic neurons exhibited movement-related activity changes. The largest proportion of single units showed modulation of firing frequency during several phases of the reach and grasp (polymodal neurons, 45/114), particularly an increase of firing rate during the reaching phase of the movement, which often correlated with movement velocity. The firing pattern (bursting, irregular, or tonic) remained unchanged during movement compared to rest. Oscillatory single unit firing activity (predominantly in the theta and beta frequency) decreased with movement onset, irrespective of oscillation frequency. This study shows for the first time specific, task-related, SUA changes during the reach-to-grasp movement in humans.
KW  - subthalamic nucleus
KW  - deep brain stimulation
KW  - Parkinson’s disease
KW  - neurophysiology
KW  - beta oscillation
KW  - reach-to-grasp movement
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170361
VL  - 11
IS  - 436
ER  - 
TY  - JOUR
A1  - Ginzkey, Christian
A1  - Eicker, Sven
A1  - Marget, Matthias
A1  - Krause, Jörg
A1  - Brecht, Stefan
A1  - Westphal, Manfred
A1  - Hugo, Heinz-Hermann
A1  - Mehdorn, Maximilian
A1  - Steinmann, Jörg
A1  - Hamel, Wolfgang
T1  - Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen
JF  - Acta Neurochirurgica
N2  - Background
Vaccination against tumour-associated antigens is one approach to elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA) vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model (9L).

Methods
Fisher 344 rats were vaccinated thrice by intramuscular injection of a lacZ-encoding or a control plasmid in weekly intervals. One week after the last vaccination, lacZ-expressing 9L cells were implanted into the striatum.

Results
After 3 weeks, in lacZ-vaccinated animals the tumours were significantly smaller than in control-vaccinated animals. In cytotoxic T cell assays lysis rates of >50 % could only be observed in a few of the lacZ-vaccinated animals. This response was directed against lacZ-expressing and parental 9L cells but not against syngeneic MADB 106 adenocarcinoma cells. In Elispot assays interferon-γ production was observed upon stimulation with 9LlacZ and 9L wild-type but not MADB 106 cells. This response was higher for lacZ-immunized animals. All animals revealed dense infiltrates with CD8+ lymphocytes and, to a lesser extent, with NK cells. CD25-staining indicated cells possibly associated with the maintenance of peripheral tolerance to self-antigens. All tumours were densely infiltrated by microglia consisting mostly of ramified cells. Only focal accumulation of macrophage-like cells expressing ED1, a marker for phagocytic activity, was observed.

Conclusion
Prophylactic DNA vaccination resulted in effective but incomplete suppression of brain tumour formation. Mechanisms other than cytotoxic T cell responses as measured in the generally used in vitro assays appear to play a role in tumour suppression.
KW  - lacZ
KW  - rat glioma
KW  - immunotherapy
KW  - DNA vaccination
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126775
VL  - 155
IS  - 1
ER  -