TY - JOUR
T1 - An electrophysiological analysis of the protective effects of felbamate, lamotrigine, and lidocaine on the functional recovery from in vitro ischemia in rat neocortical slices
AU - Siniscalchi, Antonio
AU - Zona, Cristina
AU - Guatteo, Ezia
AU - Mercuri, Nicola B.
AU - Bernardi, Giorgio
PY - 1998/12
Y1 - 1998/12
N2 - We used field potential recording techniques to examine whether felbamate (FBM), lamotrigine (LTG), and lidocaine (LID) protect against the irreversible functional damage induced by transient ischemia. Five minutes of ischemia caused a depression of the field potential in rat cortical slices, which did not recover even after more than 1 h of washout. The N-methyl-D- aspartate (NMDA) antagonist ketamine (50 μM) protected against depression of the field caused by ischemia. On the other hand, the non-NMDA antagonist 6- cyano-7-nitroquinoxaline-2.3-dione (CNQX) (10 μM) had protective effects only if co-applied with ketamine. We found that either FBM (30-300 μM), which did not modify the amplitude of the field EPSP, or LTG (10-300 μM), which reversibly depressed the excitatory synaptic transmission, had a marked protective effect when superfused before and during the ischemic insult. After FBM (100 μM) and LTG (100 μM), the field EPSP recovered by 84 ± 1% and 73 ± 2.7% of control, respectively. Furthermore, LID (30-300 μM) was less effective than FBM and LTG in inducing a functional recovery from the damage caused by ischemia (58 ± 1.8%). The rank order of potency, based on the maximal protection caused by the three drugs, was FBM > LTG > LID. Our results suggest that a noticeable neuroprotection can be obtained during glucose and O2 deprivation by preventive therapeutic regimens which use the two recently marketed anticonvulsant drugs, FBM and LTG.
AB - We used field potential recording techniques to examine whether felbamate (FBM), lamotrigine (LTG), and lidocaine (LID) protect against the irreversible functional damage induced by transient ischemia. Five minutes of ischemia caused a depression of the field potential in rat cortical slices, which did not recover even after more than 1 h of washout. The N-methyl-D- aspartate (NMDA) antagonist ketamine (50 μM) protected against depression of the field caused by ischemia. On the other hand, the non-NMDA antagonist 6- cyano-7-nitroquinoxaline-2.3-dione (CNQX) (10 μM) had protective effects only if co-applied with ketamine. We found that either FBM (30-300 μM), which did not modify the amplitude of the field EPSP, or LTG (10-300 μM), which reversibly depressed the excitatory synaptic transmission, had a marked protective effect when superfused before and during the ischemic insult. After FBM (100 μM) and LTG (100 μM), the field EPSP recovered by 84 ± 1% and 73 ± 2.7% of control, respectively. Furthermore, LID (30-300 μM) was less effective than FBM and LTG in inducing a functional recovery from the damage caused by ischemia (58 ± 1.8%). The rank order of potency, based on the maximal protection caused by the three drugs, was FBM > LTG > LID. Our results suggest that a noticeable neuroprotection can be obtained during glucose and O2 deprivation by preventive therapeutic regimens which use the two recently marketed anticonvulsant drugs, FBM and LTG.
KW - Cerebral ischemia
KW - Glucose deprivation
KW - Glutamate antagonists
KW - Neuroprotection
KW - O
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U2 - 10.1002/(SICI)1098-2396(199812)30:4<371::AID-SYN4>3.0.CO;2-V
DO - 10.1002/(SICI)1098-2396(199812)30:4<371::AID-SYN4>3.0.CO;2-V
M3 - Article
C2 - 9826229
AN - SCOPUS:0031733873
SN - 0887-4476
VL - 30
SP - 371
EP - 379
JO - Synapse
JF - Synapse
IS - 4
ER -