ReviewBlood–brain barrier breakdown-inducing astrocytic transformation: Novel targets for the prevention of epilepsy
Section snippets
Injury-related epileptogenesis: a potential role for blood–brain barrier disruption and serum-derived albumin
Focal epilepsy typically arises from neuronal tissue either within or adjacent to a cortical lesion (Willoughby, 2000). The focus of epileptic tissue is often located in the hippocampal formation within the temporal lobe (temporal lobe epilepsy, TLE). Neurosurgical removal of the epileptogenic area in many patients leads to control or even abolishment of seizures. However, in light of the high rate of drug resistant focal epilepsies, and other neurological impairments following insults to the
The role of glia cells in epileptogenesis
The interactions observed between serum albumin and astrocytes, followed by astrocytic transformation and dysfunction early during epileptogenesis suggest a key role for astrocytes in the epileptogenic process. Indeed, proliferation of astrocytes is a pathological hallmark in many patients with TLE. Recent studies have implicated novel physiological roles for glia cells in the CNS, such as modulation of synaptic transmission and plasticity. Accumulating evidence show clear changes in the
The TGFβ pathway and epileptogenesis
TGFβs are pleiotropic cytokines that play a pivotal role in intercellular communication (for review see Massague, 2000, Shi and Massague, 2003), and their signaling pathways are frequently involved in cell growth, embryogenesis, differentiation, morphogenesis, wound healing, immune response, and apoptosis in a wide variety of cells (Blobe et al., 2000, Flanders et al., 1991, Gold and Parekh, 1999). TGFβ signaling is mediated mainly by two serine threonine kinase receptors, TGFβRI and TGFβRII,
Detection of BBB damage in the human epileptic brain
Is there any evidence in human studies for the involvement of pathology at the BBB and epileptogenesis? As mentioned above, pathological and immunohistochemical studies in human epileptic tissue consistently demonstrated structural evidence for abnormal BBB and serum albumin within the neuropil and cellular elements as functional evidence for abnormal vessels permeability for large hydrophilic molecules. These data call for the development of strategies to detect BBB permeability changes for
Acknowledgments
Supported by the Sonderforschungsbereich TR3 (AF and UH), the Israeli Science Foundation (566/07, AF), the Binational US–Israel Foundation (BSF 2007185, AF and DK) and the CURE foundation (DK and AF). The authors thank Dr. Dominik Zumsteg for helping with the illustration.
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