TY - JOUR
T1 - Ischemic tolerance induction in organotypic hippocampal slices
T2 - Role for the GABAA receptor?
AU - Lange-Asschenfeldt, Christian
AU - Raval, Ami P.
AU - Pérez-Pinzón, Miguel A.
N1 - Funding Information:
This study was supported by NIH grants NS34773 and NS05820.
PY - 2005/8/12
Y1 - 2005/8/12
N2 - Ischemic preconditioning (IPC) refers to sublethal ischemic insults rendering brain tissue tolerant against subsequent ischemic insults. We investigated the role of the GABAA receptor (GABAAR) upon IPC induction. Rat organotypic hippocampal slices were subjected to IPC by 15 min of oxygen-glucose deprivation (OGD) followed by 40 min of OGD 48 h later, resulting in robust cell death reduction as assessed by the propidium iodide fluorescence method ('late' or 'second window' IPC). Superfusion with the GABAAR antagonist bicuculline during IPC ameliorated propidium iodide uptake at a high but not at low doses indicating that GABAAR activation may be assigned a limited role in neuroprotection. In previous studies, we found that increased neuronal excitability can promote IPC neuroprotection. We, therefore, tested the hypothesis that blockade of inhibitory GABAergic transmission conferred ischemic tolerance. However, temporary administration of bicuculline 48 h prior to ischemic challenge was not neuroprotective. In another approach, we tested whether preconditioning with the GABAAR agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) mediated ischemic tolerance and found no significant neuroprotection. The results are discussed in light of the intrinsic excitatory-inhibitory balance of glutamate and GABA.
AB - Ischemic preconditioning (IPC) refers to sublethal ischemic insults rendering brain tissue tolerant against subsequent ischemic insults. We investigated the role of the GABAA receptor (GABAAR) upon IPC induction. Rat organotypic hippocampal slices were subjected to IPC by 15 min of oxygen-glucose deprivation (OGD) followed by 40 min of OGD 48 h later, resulting in robust cell death reduction as assessed by the propidium iodide fluorescence method ('late' or 'second window' IPC). Superfusion with the GABAAR antagonist bicuculline during IPC ameliorated propidium iodide uptake at a high but not at low doses indicating that GABAAR activation may be assigned a limited role in neuroprotection. In previous studies, we found that increased neuronal excitability can promote IPC neuroprotection. We, therefore, tested the hypothesis that blockade of inhibitory GABAergic transmission conferred ischemic tolerance. However, temporary administration of bicuculline 48 h prior to ischemic challenge was not neuroprotective. In another approach, we tested whether preconditioning with the GABAAR agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) mediated ischemic tolerance and found no significant neuroprotection. The results are discussed in light of the intrinsic excitatory-inhibitory balance of glutamate and GABA.
KW - Bicuculline
KW - GABA receptor
KW - Ischemia
KW - Organotypic
KW - Preconditioning
KW - THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol)
UR - http://www.scopus.com/inward/record.url?scp=20444485082&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20444485082&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2005.04.053
DO - 10.1016/j.neulet.2005.04.053
M3 - Article
C2 - 15908115
AN - SCOPUS:20444485082
VL - 384
SP - 87
EP - 92
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1-2
ER -