PMID- 15730532
OWN - NLM
STAT- MEDLINE
DCOM- 20050331
LR  - 20141120
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 46
IP  - 3
DP  - 2005 Mar
TI  - Increased seizure susceptibility of the hippocampus compared with the neocortex 
      of the immature mouse brain in vitro.
PG  - 356-66
AB  - PURPOSE: The temporal lobe seems particularly susceptible to seizure activity. 
      Mesial temporal lobe structures, including the hippocampus, have the lowest 
      seizure thresholds in the brain. Conversely, thresholds in the frontal neocortex 
      are significantly higher. The development of intact, isolated preparations of 
      hippocampus and neocortex in vitro allows for study into mechanisms governing 
      seizure threshold. METHODS: Epileptiform discharges in isolated mouse neocortical 
      blocks were compared with the contralateral intact hippocampus, isolated from the 
      same brain, by using the low-Mg2+, 4 aminopyridine (4-AP), and low-Ca2+ in vitro 
      seizure models. The pharmacology of low Mg(2+)-induced ictal-like events (ILEs) 
      generated in the hippocampus and neocortex was then compared by using 
      glutamatergic antagonists DL-2-amino-5-phosphonovaleric acid (APV) and 
      6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), and the Ca2+ channel antagonist, 
      nifedipine. RESULTS: Neocortical blocks generated both recurrent, spontaneous 
      ILEs and interictal-like events under low-Mg2+ artificial CSF (aCSF) perfusion, 
      distinct from those generated in the hippocampus. ILEs from the hippocampus 
      displayed lower thresholds and longer durations as compared with isolated 
      neocortical blocks. Similar results were obtained during 4-AP perfusion. 
      Perfusion with low-Ca2+ ACSF did not produce stereotypical ILEs in the 
      neocortical block, producing instead recurrent, slow depolarizations. Both ILEs 
      and recurrent, slow depolarizations were produced in the hippocampus. Application 
      of APV and nifedipine exacerbated low Mg(2+)-induced ILEs in the hippocampus but 
      not the neocortex, indicating a distinct pharmacology for partial seizures of 
      different brain regions. CONCLUSIONS: The developing mouse hippocampus 
      demonstrates increased ictogenesis compared with the developing neocortex in 
      vitro, consistent with clinical observations and in vivo experimental models.
FAU - Abdelmalik, Peter A
AU  - Abdelmalik PA
AD  - Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
FAU - Burnham, W McIntyre
AU  - Burnham WM
FAU - Carlen, Peter L
AU  - Carlen PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Convulsants)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Animals
MH  - Calcium Channel Blockers/pharmacology
MH  - Convulsants/pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Epilepsy, Temporal Lobe/chemically induced/physiopathology
MH  - Evoked Potentials/drug effects/physiology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Frontal Lobe/drug effects/growth & development/physiopathology
MH  - Functional Laterality/drug effects/physiology
MH  - Hippocampus/*drug effects/*growth & development/physiopathology
MH  - Hypocalcemia/physiopathology
MH  - In Vitro Techniques
MH  - Magnesium Deficiency/cerebrospinal fluid/physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neocortex/*drug effects/*growth & development/physiopathology
MH  - Nifedipine/pharmacology
MH  - Seizures/*chemically induced/physiopathology
MH  - Synaptic Transmission/drug effects/physiology
EDAT- 2005/02/26 09:00
MHDA- 2005/04/01 09:00
CRDT- 2005/02/26 09:00
PHST- 2005/02/26 09:00 [pubmed]
PHST- 2005/04/01 09:00 [medline]
PHST- 2005/02/26 09:00 [entrez]
AID - EPI34204 [pii]
AID - 10.1111/j.0013-9580.2005.34204.x [doi]
PST - ppublish
SO  - Epilepsia. 2005 Mar;46(3):356-66. doi: 10.1111/j.0013-9580.2005.34204.x.