Children's Hospital New Orleans Archives

2014

Impact Grant

Dr. Chittalsinh M. Raulji

New Orleans, LA

Gliobalstoma Multiforme (GBM) is a malignant and one of the most aggressive brain tumors. It is one of the most common brain tumors overall with 9,000 cases in the US annually. Seizures are common in these type brain tumors and are very difficult to treat, which increases the morbidity and mortality. Also, some seizures may be resistant to multiple drug treatments. The seizures arise as a result of abnormal electrical activity in the peritumoral regions. The seizures cause brain damage and aggravate the outcome of GBM. Therefore, it is important to understand mechanism of seizure origin in GBM patients and to bring in modalities that can be effective in controlling seizures and reducing morbidity associated with GBM. This may act synergistically with anticancer treatment, which can improve survival as well.

Docosahexaenoic acid (DHA) is an essential fatty acid that is shown to be neuroprotectant against experimental stroke, reduces severe evoked seizures in a model of epilepsy and potentially can be beneficial in attenuating seizures induced by GBM and improving outcome. Therefore, we propose to determine the neuroprotective bioactivity of DHA in peritumoral neuronal networks in in vivo model of GBM.

Our hypothesis is that GBM induces injury in peritumoral neuronal networks that contribute to hyper-excitability and seizure susceptibility. This can be attenuated by DHA administration.

We will create a mouse model of GBM by injecting GBM cells in mice using microsurgery approach. In different experiments we will describe damage and hyper-excitability caused by GBM in peritumoral regions by means of imaging and different histological tests and EEG analysis. Next, DHA will be injected in the mice to determine if DHA decreases tumor size and seizure susceptibility. Analysis of mice brain will be done at molecular level to determine effects of DHA on GBM. We plan to finish all experiments and data analysis within 9 months of start of the project.