Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies.

Background And Purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways.

Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats.

Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research.

Concentration- and time-dependent effects of myo-inositol on evoked epileptic afterdischarge in the hippocampus in vivo.

Epilepsy is one of the most widespread neurological diseases characterized by spontaneous recurrent seizures. There is no cure for epilepsy, and available pharmacological treatments with anti-seizure drugs are only symptomatic. Moreover, about third of epilepsy patients are resistant to the anti-seizure drugs.

Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus.

Amyloid-beta (Abeta) is causally implicated in Alzheimer's disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Abeta(1-42) inhibits LTP in the dentate gyrus of rat hippocampal slices. We now show, using whole cell recordings in hippocampal granule cells, that oligomeric Abeta(1-42) decreases neuronal excitability.

Developmental changes in diffusion anisotropy coincide with immature oligodendrocyte progression and maturation of compound action potential.

Disruption of oligodendrocyte lineage progression is implicated in the white-matter injury that occurs in cerebral palsy. We have previously published a model in rabbits consistent with cerebral palsy. Little is known of normal white-matter development in perinatal rabbits.

AMPA and NMDA receptor-mediated currents in developing dentate gyrus granule cells.

Granule cells (GCs) of the hippocampal dentate gyrus (DG) undergo postnatal neurogenesis such that cells at different maturational stages can be studied within an anatomically restricted region and a narrow animal age epoch. Using whole cell patch clamp recordings in hippocampal slices, we have previously found that input resistance (IR) correlates inversely with morphometric indicators of GC maturity. Using IR as an index of maturity we measured developmental changes in synaptic currents mediated by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in GCs from 5- to 12-day rats.

ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.

Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP.

ApoE isoform affects LTP in human targeted replacement mice.

Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR.