Levetiracetam prophylaxis ameliorates seizure epileptogenesis after fluid percussion injury.
To determine whether post-traumatic seizure severity would be affected by the interval between seizures and head injury, we measured seizures after various times with or without fluid percussion brain injury (2atm fluid percussion injury; FPI). To determine efficacy of anti-seizure medication, we also determined if levetiracetam (LEV) would alter the relationship between injury and subsequent seizures. Early post-traumatic seizures were induced by Kainic acid (KA) at one week after 2atm fluid percussion injury (FPI) in one group (FPI-ES). Seizures were induced at two weeks after FPI by KA in another group (FPI-LS). In addition, one group had induced seizures by KA without FPI, (sham-ES). Finally one group of animals received the antiepileptic agent (levetiracetam) infusion for one week after FPI and then had seizures induced by KA (FPI-LEV-ES). We measured seizure onset time, ictal duration and severity of seizures using a modified Racine's scale. Histopathological changes in the hippocampus CA1 region were also analyzed. Severity of seizures were increased in the FPI-ES group compared with sham-ES animals. Severity was also enhanced in early post-injury seizures induced by KA (FPI-ES vs. FPI-LS); this exacerbation of seizure severity could be ameliorated by levetiracetam infusion (FPI-ES vs. FPI-LEV-ES). Neuronal degeneration in CA1 was more severe in the FPI-ES group and this degeneration was also diminished by LEV. We conclude that early post injury seizures exacerbate susceptibility and severity of post traumatic seizures and increase neuronal degeneration in the CA1 layer of hippocampus. These changes are partially reversed by LEV infusion after FPI.
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address: chenyh178@gmail.com.
Yuan-Hao
YH
Chen
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Eagle Yi-Kung
EY
Huang
Graduate Institute of Computer and Communication Engineering, National Taipei University of Technology, Taipei, Taiwan, ROC.
Tung-Tai
TT
Kuo
Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; Graduate Program on Neuroregeneration, Taipei Medical University, Taipei, Taiwan, ROC.
Barry J
BJ
Hoffer
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Pei-Jie
PJ
Wu
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Hsin-I
HI
Ma
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Jing-Jr
JJ
Tsai
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Yu-Ching
YC
Chou
Graduate Program on Neuroregeneration, Taipei Medical University, Taipei, Taiwan, ROC.
Yung-Hsiao
YH
Chiang
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004834:Epilepsy, Post-Traumatic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007608:Kainic Acid; D000077287:Levetiracetam; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013997:Time Factors
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D000077287:Levetiracetam; D007608:Kainic Acid; D010889:Piracetam
Levetiracetam; Seizures; Traumatic brain injury