Article

Effects of levetiracetam on blood-brain barrier disturbances following hyperthermia-induced seizures in rats with cortical dysplasia

Department of Histology and Embryology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Life sciences (Impact Factor: 2.3). 09/2010; 87(19-22):609-19. DOI: 10.1016/j.lfs.2010.09.014
Source: PubMed

ABSTRACT The mechanisms underlying the changes in blood-brain barrier (BBB) integrity and the generation of seizures in childhood associated with preexisting brain lesions like cortical dysplasia (CD) are poorly understood. We investigated the effects of levetiracetam (LEV) on BBB integrity and the survival during hyperthermic seizures in rats with CD.
Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. On postnatal day 28, hyperthermia-induced seizures were evoked in offspring with CD. To show the functional and morphological alterations in BBB integrity, quantitative analysis of sodium fluorescein (NaFlu) extravasation, immunohistochemistry and electron microscopy were performed.
Seizure scores and mortality rates were decreased by LEV during hyperthermia-induced seizures in rats with CD (P<0.01). Increased NaFlu extravasation into brain by hyperthermia-induced seizures in animals with CD was decreased by LEV (P<0.01). While glial fibrillary acidic protein (GFAP) immunoreactivity slightly increased in brain sections of animals with CD during hyperthermia-induced seizures, LEV led to GFAP immunoreactivity comparable to that of controls. Decreased occludin immunoreactivity and expression in CD plus hyperthermia-induced seizures was increased by LEV. Opening of tight junctions and abundance of pinocytotic vesicles representing ultrastructural evidences of BBB impairment and severe perivascular edema were observed in animals with CD exposed to hyperthermia-induced seizures and LEV treatment led to the attenuation of these findings.
These results indicate that LEV may present a novel approach for the protection of the BBB besides its antiepileptic impact on hyperthermic seizures in the setting of CD.

Download full-text

Full-text

Available from: Candan Gürses, Apr 22, 2014
0 Followers
 · 
265 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The blood–brain barrier (BBB) is a dynamic and complex system which separates the brain from the blood. It helps to maintain the homeostasis of the brain, which is essential for normal neuronal functioning. BBB function is impaired in several neurological diseases, including epilepsy in which it may lead to abnormal and excessive neuronal firing. In this review we will discuss how BBB dysfunction can affect neuronal function and how this can lead to seizures and epilepsy. We will also summarize new therapies that aim to preserve or restore BBB function in order to prevent or reduce epileptogenesis.
    Seminars in Cell and Developmental Biology 11/2014; DOI:10.1016/j.semcdb.2014.10.003 · 5.97 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: SUMMARY 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. KEY WORDS: Cortical dysplasia, Epilepsy, Blood– brain barrier, Electron microscopy, Immunohistochemistry, Lesion with vascular component
    Epilepsia 01/2012; · 4.58 Impact Factor