Abstract:
:Spreading depression (SD) is characterized by a transient breakdown of neuronal function concomitant with a massive failure of ion homeostasis. It is a phenomenon that can be induced in neocortical tissue by raising excitability, e.g. injection of K(+), application of glutamatergic agonists, or blocking Na(+)/K(+) ATPase. Here we report a novel method of SD induction using minimal disinhibition with application of low concentrations (5 microM) of the GABA(A) receptor blocker bicuculline. This procedure-while subthreshold for epileptiform activity-readily induced spontaneous SDs in native rat neocortical slices, accompanied by typical depolarizations of neurons and glial cells. In contrast, in human neocortical preparations obtained from epilepsy surgery, in approximately 20% of the slices spontaneous epileptiform activity appeared with this bicuculline dosage without SDs. Raising the concentration of bicuculline to an epileptogenic dose (10 microM) in human tissue also resulted in the generation of epileptiform activity only. Likewise, in slices from pilocarpine-treated, chronically epileptic rats, bicuculline also only induced epileptiform activity without eliciting SDs. The experiments indicate that chronic epilepsy causes a differential sensitivity to partial GABA(A) receptor blockade with regard to induction of SD.
journal_name
Brain Resjournal_title
Brain researchauthors
Köhling R,Koch UR,Hagemann G,Redecker C,Straub H,Speckmann EJdoi
10.1016/s0006-8993(03)02600-3subject
Has Abstractpub_date
2003-06-13 00:00:00pages
129-34issue
1-2eissn
0006-8993issn
1872-6240pii
S0006899303026003journal_volume
975pub_type
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