189 research outputs found
The Free Radical Scavenger N-Tert-Butyl-α-Phenylnitrone (PBN) Administered to Immature Rats During Status Epilepticus Alters Neurogenesis and Has Variable Effects, Both Beneficial and Detrimental, on Long-Term Outcomes
Status epilepticus (SE), especially in immature animals, is known to produce recurrent spontaneous seizures and behavioral comorbidities later in life. The cause of these adverse long-term outcomes is unknown, but it has been hypothesized that free radicals produced by SE may play a role. We tested this hypothesis by treating immature (P25) rats with the free radical scavenger N-tert-butyl-α-phenylnitrone (PBN) at the time of lithium chloride (LiCl)/pilocarpine (PILO)-induced SE. Later, long-term outcomes were assessed. Cognitive impairment (spatial memory) was tested in the Morris water maze (MWM). Emotional disturbances were assessed by the capture test (aggressiveness) and elevated plus maze’s (EPM) test (anxiety). Next, the presence and severity of spontaneous seizures were assessed by continuous video/EEG monitoring for 5 days. Finally, immunochemistry, stereology and morphology were used to assess the effects of PBN on hippocampal neuropathology and neurogenesis. PBN treatment modified the long-term effects of SE in varying ways, some beneficial and some detrimental. Beneficially, PBN protected against severe anatomical damage in the hippocampus and associated spatial memory impairment. Detrimentally, PBN treated animals had more severe seizures later in life. PBN also made animals more aggressive and more anxious. Correlating with these detrimental long-term outcomes, PBN significantly modified post-natal neurogenesis. Treated animals had significantly increased numbers of mature granule cells (GCs) ectopically located in the dentate hilus (DH). These results raise the possibility that abnormal neurogenesis may significantly contribute to the development of post-SE epilepsy and behavioral comorbidities
LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition
Wolf-Hirschhorn syndrome (WHS) represents an archetypical example of a contiguous gene deletion disorder – a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes,incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca2+] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarizationand superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHScohort. Our findings identify novel cellular phenotypes in WHSattributable to a 50% reduction in LETM1 expression level; thesephenotypes could underlie and/or contribute to some of the core clinical features of this condition
Technical and experimental features of Magnetic Resonance Spectroscopy of brain glycogen metabolism
When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?
The influence of L-methionine-D,L-sulfoximine on the labelling of acid soluble fraction and proteins of the brain cortex after intraperitoneal injection of 14C-leucine
Cerebral Metabolic State after Discontinuation of Nitrous Oxide Supply in Artificially Ventilated Rats
Influence of phenobarbital on changes in the metabolites of the energy reserve of the cerebral cortex following complete ischemia
Behavioral and Metabolic Changes in Immature Rats during Seizures Induced by Homocysteic Acid: The Protective Effect of NMDA and Non-NMDA Receptor Antagonists
Restitution of Cerebral Energy State after Complete and Incomplete Ischemia of 30 min Duration
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