Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics

Abstract

Status epilepticus (SE) affects approximately 41 of every 100 000 adults and is difficult to treat. For this reason, up to 20% of cases are reported to involve mortality. 1 Various neurological disorders are associated with SE, including cerebrovascular diseases, trauma, intoxication, and also others, but it is unclear why SE develops only in some patients affected by the previously mentioned central nervous system (CNS) disorders. In addition, SE also develops without a clear reason in some cases. Finally, patients with epilepsy may experience one or more episodes of SE, whereas others

Antiepileptogenic effects of trilostane in the kainic acid model of temporal lobe epilepsy

“…We did not observe any effect of trilostane administration on the investigated features of SE induced by KA. This finding was at odds with our previously reported result, in which KA‐treated rats that received two trilostane injections before the SE induction presented an anticipated disappearance of convulsive seizures 21 . The difference between the present and previous studies suggests that trilostane could not be effective in counteracting the seizures when administered after SE onset.…”

Relationship between Delta Rhythm, Seizure Occurrence and Allopregnanolone Hippocampal Levels in Epileptic Rats Exposed to the Rebound Effect

“…Particularly, tolerance to LEV could be a result of functional adaptation of LEV's target(s) to the presence of the AED, which might result in increased seizure frequency after AED discontinuation. However, in the attempt to define a risk index for the rebound effect after rapid AED withdrawal, our animal model could be useful [17,18,32], since our animals developed an abrupt increase of generalized tonic-clonic SRSs, after LEV discontinuation. Alternatively, other mechanisms could contribute to the rebound effect, in particular the time window in which specific brain areas might be interested by neurogenesis [33].…”

Allopregnanolone: An overview on its synthesis and effects

“…In this context, it is important to highlight that neuroactive steroids represent an important target for the treatment of focal epileptic disorders 242 . Indeed, alteration of ALLO synthesis modulate status epilepticus dynamics 243,244 . In addition, protective effects have been reported in an experimental model of amyotrophic lateral sclerosis (ie, Wobbler mouse), 245 in PD experimental models, 246,247 as well as in a pilot clinical study performed in patients affected by fragile X‐associated tremor/ataxia syndrome, where the ALLO treatment was reported to improve cognitive function and neurodegeneration 248,249 …”

“…242 Indeed, alteration of ALLO synthesis modulate status epilepticus dynamics. 243,244 In addition, protective effects have been reported in an experimental model of amyotrophic lateral sclerosis (ie, Wobbler mouse), 245 in PD experimental models, 246,247 as well as in a pilot clinical study performed in patients affected by fragile X-associated tremor/ataxia syndrome, where the ALLO treatment was reported to improve cognitive function and neurodegeneration. 248,249 In an animal model of Niemann-Pick type C disease, this neuroactive steroid has been demonstrated to delay the onset of neurological symptoms, increasing Purkinje and granule cell survival in the cerebellum, reducing cortical ganglioside accumulation, cholesterol accumulation and inflammation, and enhancing myelination.…”