TY - JOUR
T1 - An animal model of generalized nonconvulsive status epilepticus
T2 - Immediate characteristics and long-term effects
AU - Wong, Michael
AU - Wozniak, David F.
AU - Yamada, Kelvin A.
N1 - Funding Information:
The authors thank Nick Rensing for technical assistance with the histology and Anna Pieper, Adam Myenberg, and Anthony Nardi for their help in the behavioral testing of the animals. This work was supported by NIH Neurological Sciences Academic Development Award 5K12NS0169004 (MW) and AG11355 (DFW).
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Absence seizures are traditionally believed to have no significant long-term neurological consequences, but few basic scientific studies have examined the effects of absence seizures on neuronal function, especially regarding absence status epilepticus. We developed a model of generalized nonconvulsive status epilepticus (GNCSE) in rats to study behavioral, functional, and histological effects of GNCSE. Using repetitive timed injections of low-dose pentylenetetrazol (PTZ), a state of prolonged behavioral arrest and immobility associated with frequent generalized spike-wave discharges on EEG could be induced for hours, consistent with GNCSE. GNCSE occurred reproducibly in adult rats, but surprisingly not in juvenile rats or adult mice. There was no evidence of pathological damage following GNCSE using Fluoro-Jade B and Cresyl Violet histological methods. Although a transient, subtle deficit in place learning occurred in PTZ-treated rats, there were no long-term behavioral effects of GNCSE on spatial learning or sensorimotor function. However, 1 week after a single episode of GNCSE, there was an increase in absence seizures in response to a repeat dose of PTZ compared to controls. These results indicate that an animal model of GNCSE can be generated and that even in the absence of overt neuronal damage, GNCSE may produce functional changes in neurons that alter electrical excitability of neural circuits.
AB - Absence seizures are traditionally believed to have no significant long-term neurological consequences, but few basic scientific studies have examined the effects of absence seizures on neuronal function, especially regarding absence status epilepticus. We developed a model of generalized nonconvulsive status epilepticus (GNCSE) in rats to study behavioral, functional, and histological effects of GNCSE. Using repetitive timed injections of low-dose pentylenetetrazol (PTZ), a state of prolonged behavioral arrest and immobility associated with frequent generalized spike-wave discharges on EEG could be induced for hours, consistent with GNCSE. GNCSE occurred reproducibly in adult rats, but surprisingly not in juvenile rats or adult mice. There was no evidence of pathological damage following GNCSE using Fluoro-Jade B and Cresyl Violet histological methods. Although a transient, subtle deficit in place learning occurred in PTZ-treated rats, there were no long-term behavioral effects of GNCSE on spatial learning or sensorimotor function. However, 1 week after a single episode of GNCSE, there was an increase in absence seizures in response to a repeat dose of PTZ compared to controls. These results indicate that an animal model of GNCSE can be generated and that even in the absence of overt neuronal damage, GNCSE may produce functional changes in neurons that alter electrical excitability of neural circuits.
KW - Absence seizure
KW - Kindling
KW - Neuronal death
KW - Pentylenetetrazol
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=0042763689&partnerID=8YFLogxK
U2 - 10.1016/S0014-4886(03)00099-2
DO - 10.1016/S0014-4886(03)00099-2
M3 - Article
C2 - 12957492
AN - SCOPUS:0042763689
SN - 0014-4886
VL - 183
SP - 87
EP - 99
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -