Determinants of drug brain uptake in a rat model of seizure-associated malformations of cortical development

Continuous neurodegeneration and death pathway activation in neurons and glia in an experimental model of severe chronic epilepsy

“…To address the relationship between the recurrence of seizures and the occurrence of cell death, we exploited here an experimental model of acquired FCD, the metylazoxymethanol/pilocarpine rat (MAM-PILO or MP rat, Colciaghi et al, 2011;Marchi et al, 2006) generated in our lab. In particular, by analyzing MP rats at different time points after SE induction (from few hours up to 6 months after epilepsy onset) we verified (through Fluoro-Jade, caspase-3, and c-Jun labeling) when, where, and how cell death occurred in neurons or glia.…”

Cerebrovascular Remodeling and Epilepsy

“…In cases of symptomatic drug-resistant epilepsies, malformations of cortical development (MCD, (Shorvon 2011a, 2011b; Spreafico and Blumcke 2010) represent a common etiological factor underlying seizures. Although aberrant neuronal circuitry was proposed to be the sole cause of hyper-excitability in the malformed brain areas, experimental evidence exists supporting the presence and role for ectopic BBB microvessels (Fan and others 2008; Hallene and others 2006; Marchi and others 2006). …”

“…Accompanying neuronal ectopias is the loss of radial cortical vessels. In addition, BBB microvessels have a tortuous morphology and are leaky to fluorescent tracers (Marchi and others 2006). MAM rats have a lower seizure threshold and seizures elicited in the MAM brain are associated with a greater extent of BBB leakage compared with seizures induced in naïve animals (Chevassus-Au-Louis and others 1998; Chevassus-Au-Louis and others 1999; Tschuluun and others 2011).…”

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).…”