Nature
March 2025
Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients' brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA.
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November 2024
Objective: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.
Methods: Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory.
Objective: Infantile spasms are associated with a wide variety of clinical conditions, including perinatal brain injuries. We have created a model in which prolonged infusion of tetrodotoxin (TTX) into the neocortex, beginning in infancy, produces a localized lesion and reproduces the behavioral spasms, electroencephalogram (EEG) abnormalities, and drug responsiveness seen clinically. Here, we undertook experiments to explore the possibility that the growth factor IGF-1 plays a role in generating epileptic spasms.
View Article and Find Full Text PDFObjective: Epileptic spasms are a hallmark of a severe epileptic state. A previous study showed neocortical up and down states defined by unit activity play a role in the generation of spasms. However, recording unit activity is challenging in clinical settings, and more accessible neurophysiological signals are needed for the analysis of these brain states.
View Article and Find Full Text PDFStudies were undertaken to evaluate the effectiveness of Acthar® Gel (repository corticotropin injection [RCI]) in the tetrodotoxin (TTX) model of early-life-induced epileptic spasms. Repository corticotropin injection (RCI) is widely used in the United States to treat infantile spasms. A major component of RCI is N25 deamidated ACTH.
View Article and Find Full Text PDFObjective: Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here.
Methods: In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms.
Neutrophil migration to the site of bacterial infection is a critical step in host defense. Exclusively produced in the bone marrow, neutrophil release into the blood is tightly controlled. Although the chemokine CXCL1 induces neutrophil influx during bacterial infections, its role in regulating neutrophil recruitment, granulopoiesis, and neutrophil mobilization in response to lung infection-induced sepsis is unclear.
View Article and Find Full Text PDFAbnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs.
View Article and Find Full Text PDFWhile infantile spasms is the most common catastrophic epilepsy of infancy and early-childhood, very little is known about the basic mechanisms responsible for this devastating disorder. In experiments reported here, spasms were induced in rats by the chronic infusion of TTX into the neocortex beginning on postnatal days 10-12. Studies of focal epilepsy suggest that high frequency EEG oscillations (HFOs) occur interictally at sites that are most likely responsible for seizure generation.
View Article and Find Full Text PDFThe effects recurring seizures have on the developing brain are an important area of debate because many forms of human epilepsy arise in early life when the central nervous system is undergoing dramatic developmental changes. To examine effects on glutamatergic synaptogenesis, epileptiform activity was induced by chronic treatment with GABAa receptor antagonists in slice cultures made from infant rat hippocampus. Experiments in control cultures showed that molecular markers for glutamatergic and GABAergic synapses recapitulated developmental milestones reported previously in vivo.
View Article and Find Full Text PDFRecurrent seizures in animal models of early-onset epilepsy have been shown to produce deficits in spatial learning and memory. While neuronal loss does not appear to underlie these effects, dendritic spine loss has been shown to occur. In experiments reported here, seizures induced either by tetanus toxin or flurothyl during the second postnatal week were found to reduce the expression of NMDA receptor subunits in both the hippocampus and neocortex.
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