title: Blood-brain barrier, epileptogenesis, and treatment strategies in cortical dysplasia.
abstract: Cortical dysplasia (CD) is one of the most important causes of intractable epilepsy. The precise mechanisms of epileptogenesis in CD are not known. Using CD animal models, we attempted to understand the mechanisms and efficacy of various antiepileptic drugs. In two separate studies, we assessed (1) the effects of levetiracetam (LEV) and vagus nerve stimulation (VNS) on pentylenetetrazol (PTZ)-kindled rats, and (2) the effects of LEV and topiramate (TPM) on rats with CD and hyperthermia (HT). In the HT-induced rats with CD study, LEV and TPM decreased both the intensity of seizures and the number of rats with seizure. In these studies, we used immunocytochemistry (occludin, glial fibrillary acidic protein [GFAP], and P-glycoprotein [Pgp antibodies] and electron microscopy (EM) (sodium fluorescein [NaFlu]) and horseradish peroxidase [HRP]) to assess blood-brain barrier (BBB) integrity. Both LEV and TPM protected BBB. In PTZ- kindled rats with CD, both LEV and VNS reduced the duration of seizures. Immunocytochemistry and EM revealed no BBB impairment in any of the treatment groups. In a second set of experiments, we assessed the relationship between disruption of vascular components and epileptogenesis. Astrocytic albumin uptake in focal epileptogenic lesions with vascular components suggested that dysfunction of the BBB contributes immediately to epileptogenesis, rather than simply resulting from seizure activity. Hemosiderin deposits were seen as potential epileptogenic triggers in vascular malformations (e.g., cavernomas [CA] or arteriovenous malformations [AVMs] with or without a dysplastic cortical component). However, we found strikingly high accumulation of astrocytic albumin deposits in surgically removed brain parenchyma in the vicinity of CAs and AVMs from patients with pharmacoresistant epilepsy, which suggests different pathophysiologic dispersion pathways for hemosiderin and albumin in vascular lesions.
authors.affiliation: Department of Physiology, Istanbul Faculty of Medicine, Epilepsy Center (EPIMER), Istanbul University, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Candan
authors.initials: C
authors.lastname: Gürses
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000502:physiology*; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D054220:Malformations of Cortical Development / Q000150:complications* / Q000503:physiopathology; D051381:Rats
chemical_list: D000927:Anticonvulsants