title: Locally applied valproate enhances survival in rats after neocortical treatment with tetanus toxin and cobalt chloride.
abstract: OBJECTIVE
  In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl₂).
  
  
  METHODS
  In rats, VPA (n = 5) or sodium chloride (NaCl) (n = 5) containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl₂. Video-EEG monitoring was performed with intracortical depth electrodes.
  
  
  RESULTS
  All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (P < 0.01). In both groups, witnessed deaths occurred in the context of seizures. At least 3/4 of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures.
  
  
  CONCLUSIONS
  The novel TeT/CoCl₂ approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.
authors.affiliation: Epilepsy Center, Department of Neurosurgery, University Hospital Freiburg, Breisacher Straße 64, 79106 Freiburg, Germany.
authors.forename: Dirk-Matthias
authors.initials: DM
authors.lastname: Altenmüller
authors.forename: Jonas M
authors.initials: JM
authors.lastname: Hebel
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rassner
authors.forename: Silvanie
authors.initials: S
authors.lastname: Volz
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Freiman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Feuerstein
authors.forename: Josef
authors.initials: J
authors.lastname: Zentner
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013744:Tetanus Toxin / Q000494:pharmacology; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D000927:Anticonvulsants; D013744:Tetanus Toxin; D003035:Cobalt; D014635:Valproic Acid; C018021:cobaltous chloride