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Human brain slices for epilepsy research: Pitfalls, solutions and future challenges

Lookup NU author(s): Anderson Brito Da Silva, Dr Roger Whittaker, Professor Mark Cunningham

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Abstract

Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits.


Publication metadata

Author(s): Jones RS, daSilva AB, Whittaker RG, Woodhall GL, Cunningham MO

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience Methods

Year: 2016

Volume: 260

Pages: 221-232

Print publication date: 15/02/2016

Online publication date: 03/10/2015

Acceptance date: 23/09/2015

ISSN (print): 0165-0270

ISSN (electronic): 1872-678X

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.jneumeth.2015.09.021

DOI: 10.1016/j.jneumeth.2015.09.021

PubMed id: 26434706


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