Abstracts

RATIONALE: Gliomas very often cause seizures as one of their first symptoms. It is largely unknown which functional changes of neuronal activity are responsible for this, and to which extent the degree of tumour invasion correlates to the changes in neuronal excitabiltiy. This study addresses the question whether the spread of activity in neuronal networks is changed by neoplastic glial cells.
METHODS: Gliomas were induced in adult Wistar rats (n=17) by stereotactic intracortical implantation of a C6 tumour cell line suspension (10 [mu]l; cell concentration: 2x10 [arrowup] 5 / [mu]l) stably transfected with GFP or LacZ. Gliomas were left to develop for 14-17 days. After this period, animals were sacrificed, and coronal neocortical slices (500 [mu]m) were made. Evoked (single electical stimuli, white matter), as well as spontaneous or triggered epileptiform activity (0-Mg2+) was monitored using the voltage-sensitive dye RH 795. Age-matched animals (n=6) served as controls.
RESULTS: Implantation of tumour cell suspension led to development of intracortical gliomas in all cases, with both solid tumours and a surrounding 200-300 [mu]m wide zone of dispersed invasion. Single electrical stimuli resulted in supragranular activation in control tissue. By contrast, in glioma-invaded slices, network activity was generally extending also to infragranular layers. Whereas in control slices, spontaneous epileptiform activity could start in any area of the neocortex, initiation sites in glioma-invaded tissue were always paratumoral.
CONCLUSIONS: These results show that glioma infiltration causes substantial alterations in network activity patterns.
[Supported by: DFG KO 1779/4-1]