Table 1.
Summary of mechanisms that may affect neuronal behavior after BBB disruption
| Mechanism or molecule | Role of BBB in mechanism | Evidence for | Evidence against |
|---|---|---|---|
| Extracellular K+ | Serum [K]>Brain [K] (Davson & Segal, 1995) | Kir knock-out mice exhibit low seizure threshold (Djukic et al., 2007) Extracellular potassium increases excitability (Janigro et al., 1997; Emmi et al., 2000; Hinterkeuser et al., 2000; Schroder et al., 2000; Kofuji & Newman, 2004; Tate & Sisodiya, 2007; Olsen & Sontheimer, 2008; Zhang & Verkman, 2008; Steinhauser & Seifert, 2010; Stewart et al., 2010; Pardini et al., 2011) |
Osmotic BBBD in rats did not cause increased [K+]out (Somjen et al., 1991) |
| Negligible K+ permeability across BBB (Stanness et al., 1996) | Potassium causes seizures when directly applied (Traynelis & Dingledine, 1988; Trombin et al., 2011) | ||
| Loss of potassium homeostasis in human epileptic brain (Bordey & Sontheimer, 1998; Heinemann et al., 2002; Steinhauser & Seifert, 2010) | |||
| Magnesium | Serum [Mg]<Brain [Mg] | Low magnesium causes epileptiform activity; high serum Mg is neuroprotective (Amtorp & Sorensen, 1974; Zhang et al., 1995) | |
| Serum albumin in astrocytes | Albumin quotient (serum>brain) | TGF-β receptor-mediated albumin uptake in neocortical epileptogenesis (Ivens et al., 2007; Cacheaux et al., 2009; David et al., 2009b) | Present in neurons less so in glia in human epilepsy (Marchi et al., 2010b,c) |
| Glutamate | Serum levels<brain levels (Smith, 2000) | Link with TGF-β and albumin (Ivens et al., 2007; Cacheaux et al., 2009; David et al., 2009b) | |
| Causes seizures and is elevated in brain of epileptics |