Age-dependent vascular changes induced by status epilepticus in rat forebrain: Implications for epileptogenesis

Brain Autonomous Mechanisms of Seizure-Induced BBB Dysfunction

“…The authors speculate that vessel remodeling has a neuroprotective function by improving the neurovascular coupling during seizures. Although this might be the case, it remains to be established whether or not the newly formed vessels are intact or "leaking" as suggested by previous in vivo evidence (6,13).…”

“…This concept has arisen from experimental evidence showing that BBB damage experimentally induced by bile salt application to the rat cortex results in delayed development of spontaneous and long-lasting epileptiform activity in brain tissue adjacent to the vascular damaged area (2). This alteration in neuronal network excitability is mimicked by cortical application of serum albumin, which is known to extravasate in the brain parenchyma due to BBB breakdown caused by seizures, status epilepticus or by various epileptogenic events such as trauma, stroke, infection (1,(3)(4)(5)(6). Further investigations unveiled one molecular mechanism pivotally involved in hyperexcitability induced by albumin extravasation, namely, the transforming growth factor (TGF)-β1 signaling activated by albumin in perivascular astrocytes.…”

Modulation of Immunity and the Inflammatory Response: A New Target for Treating Drug-resistant Epilepsy

“…The activation of IL-1R/TLR signaling mediates rapid post-translational changes in N-methyl-d-aspartate(NMDA)-gated inward Ca 2+ channels in pyramidal neurons. IL-1Rs are colocalizes with NMDA receptors on dendrites of neurons [52];Inflammatory mediators can also increase vascular permeability and promote angiogenesis [53]. Thus, their overexpression in perivascular astrocytes and endothelial cells after epileptogenic challenges may affect BBB properties, consequently promoting excitability in surrounding neurons [54];…”

“…Inflammatory mediators can also increase vascular permeability and promote angiogenesis [53]. Thus, their overexpression in perivascular astrocytes and endothelial cells after epileptogenic challenges may affect BBB properties, consequently promoting excitability in surrounding neurons [54];…”

“…The phenomenon above is not only associated with inflammatory processes but also with alterations in astrocytic properties that impact on the DRE state [81]. Quite remarkably, in epileptic patients whose intracranial encephalographies showed several spontaneous seizures originating in the hippocampus, which was subsequently resected, the proportion of seizures was directly correlated with glia density in the hippocampal CA3 area, and electrical seizure duration was directly correlated with the glia density in CA2 and CA3 areas, whereas hippocampal neuronal counts did not correlate with any EEG variables [130].…”