BRIDGING THE GAP – BENEFITS OF NEUROSURGICAL TISSUE FOR PRE-CLINICAL RESEARCH

Abstract

The use of primary human neural tissue for research provides an invaluable insight into human neural function that cannot be achieved in any other way. Despite this it is successfully collected and used in only a small minority of units. We have established a collaboration between the Wessex Neurological Centre and the University of Southampton that allows us to study using human tissue resected during neurosurgery, and have used this tissue for over a decade. Tissue is most commonly collected from oncological, epilepsy and vascular operations. Here we share our experiences of the practicalities of working with live human glioma tissue and try to provide some insights for practicing neuro-oncology surgeons. We discuss the ethical considerations and practical difficulties of the co-ordination of the clinical and academic teams, and challenge of optimization of the tissue for the research. We will present the mechanisms in place to optimize the study of human neural tissue. We will review the progression from resection of tissue from glioma surgery to epilepsy surgery to any neurosurgical procedure in which the normal brain is resected and tissue discarded. We discuss the different models that can be used and the application locally to glioma stem cells, pathways activated in TBI, tissue damage from haemoglobin, the electrophysiology of the normal brain and with age and the inflammatory response of microglia. We will present examples of the value of human tissue studies. Firstly we will show the importance of primary glioma tissue compared to established glioma cell lines. Secondly, we will demonstrate some electrophysiological differences between humans and rodent that could only be investigated through the use of live human tissue obtained at operation. We will also demonstrate how we have moved to streamline tissue collection and propose a move to establish a national framework for such experiments.