title: A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid.
abstract: OBJECTIVE
  Models of temporal lobe epilepsy are commonly utilized to study focal epileptogenesis and ictogenesis. The criteria that define animal models representative of human mesial temporal lobe may vary in different laboratories. We describe herein a focal epilepsy model of mesial temporal (hippocampal) origin that relies on the analysis of interictal and ictal electroencephalography (EEG) patterns and on their correlation with seizure symptoms and neuropathologic findings. The study is based on guinea pigs, a species seldom utilized to develop chronic epilepsy models.
  
  
  METHODS
  Young adult guinea pigs were bilaterally implanted under isoflurane anesthesia with epidural electrodes over somatosensory cortex and depth electrodes in CA1 hippocampal region. A stainless steel guide cannula was positioned unilaterally in the right dorsal hippocampus to inject 1 μl of 0.9% NaCl solution containing 1 μg kainic acid (KA). One week after surgery, continuous 24 h/day video-EEG monitoring was performed 48 h before and every other week after KA injection, for no <1 month. EEG data were recorded wide-band at 2 kHz. After video-EEG monitoring, brains were analyzed for thionine and Timm staining and glial fibrillary acid protein (GFAP) immunostaining.
  
  
  RESULTS
  Unilateral injection of KA in dorsal hippocampus of guinea pigs induces an acute nonconvulsive status epilepticus (SE) that terminates within 24 h (n = 22). Chronic seizures with very mild motor signs (undetectable without EEG monitoring) and highly variable recurrence patterns appear in 45.5% (10 of 22) KA-treated animals, with variable delays from the initial SE. In these animals interictal events, CA1 cell loss, gliosis, and altered Timm staining pattern were observed. The induction of a chronic condition did not correlate with the duration of the nonconvulsive acute SE, but correlated with the extension and quality of neuropathologic damage.
  
  
  CONCLUSIONS
  We demonstrate that a model of hippocampal (mesial temporal lobe) epilepsy can be developed in the guinea pig by intrahippocampal injection of KA. Seizure events in this model show little behavioral signs and may be overlooked without extensive video-EEG monitoring. The establishment of a chronic epileptic condition correlates with the extension of the hippocampal damage (mainly cell loss and gliosis) and not with the intensity of the initial SE.
authors.affiliation: Unit of Epileptology and Experimental Neurophysiology, The Foundation of the Carlo Besta Neurological Institute, via Amadeo 42, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Carriero
authors.forename: Salvatore
authors.initials: S
authors.lastname: Arcieri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cattalini
authors.forename: Laura
authors.initials: L
authors.lastname: Corsi
authors.forename: Vadym
authors.initials: V
authors.lastname: Gnatkovsky
authors.forename: Marco
authors.initials: M
authors.lastname: de Curtis
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*
chemical_list: D007608:Kainic Acid