A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats.
Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66+/-37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies.
Kharatishvili
I
I
Epilepsy Research Laboratory, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, and Department of Neurology, Kuopio University Hospital, Finland.
Nissinen
J P
JP
McIntosh
T K
TK
Pitkänen
A
A
D000818:Animals; D001049:Apnea / Q000209:etiology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001924:Brain Concussion / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D020439:Growth Cones / Q000473:pathology / Q000502:physiology; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors