PMID- 10708680
OWN - NLM
STAT- MEDLINE
DCOM- 20000424
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 858
IP  - 2
DP  - 2000 Mar 10
TI  - Spatio-temporal profile of DNA fragmentation and its relationship to patterns of 
      epileptiform activity following focally evoked limbic seizures.
PG  - 290-302
AB  - The specific electrographic activity responsible for seizure-induced DNA damage 
      remains little explored. We therefore examined the regional and temporal 
      appearance of DNA fragmentation and cell death and its relationship to specific 
      electrographic seizure patterns in a rat model of focally evoked limbic epilepsy. 
      Animals received intra-amygdaloid injection of kainic acid (KA) to induce 
      seizures for 45 min during continuous electroencephalographic (EEG) monitoring, 
      after which diazepam (30 mg/kg) was administered. DNA polymerase I-mediated 
      biotin-dATP nick translation (PANT) and terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) were used to detect single- 
      and double-stranded DNA breaks, respectively. Injection of 0.01 microg KA induced 
      seizures characterized by ictal fast activity but without consequent brain 
      injury. By contrast, 0.1 microg KA induced an additional pattern of seizure 
      activity characterized by bursts of high frequency polyspike paroxysmal 
      discharges. In these animals, there was a significant reduction in numbers of 
      pyramidal neurons within the ipsilateral and contralateral CA3 subfield of the 
      hippocampus, detectable as little as 4 h following seizures. PANT- and 
      TUNEL-positive cells appeared in similar numbers 16 h following seizure cessation 
      within the CA3, declining after 72-96 h. Varying the duration of polyspike 
      paroxysmal discharges determined that as little as 30 s elicited maximal injury. 
      These data suggest single- and double-stranded DNA breaks are generated during 
      the cell death process and are consequent on a specific component of seizure 
      activity electrographically determined.
FAU - Henshall, D C
AU  - Henshall DC
AD  - Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. 
      dhenshal@lhs.org
FAU - Sinclair, J
AU  - Sinclair J
FAU - Simon, R P
AU  - Simon RP
LA  - eng
GR  - NS24728/NS/NINDS NIH HHS/United States
GR  - NS39016/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - *DNA Fragmentation
MH  - Disease Models, Animal
MH  - Electroencephalography
MH  - Epilepsy/chemically induced/*pathology/physiopathology
MH  - Excitatory Amino Acid Agonists
MH  - Functional Laterality
MH  - Hippocampus/*pathology/physiopathology
MH  - In Situ Nick-End Labeling
MH  - Kainic Acid
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2000/03/10 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/03/10 09:00
PHST- 2000/03/10 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/03/10 09:00 [entrez]
AID - S0006-8993(99)02452-X [pii]
AID - 10.1016/s0006-8993(99)02452-x [doi]
PST - ppublish
SO  - Brain Res. 2000 Mar 10;858(2):290-302. doi: 10.1016/s0006-8993(99)02452-x.