Long‐term alterations in glutamate receptor and transporter expression following early‐life seizures are associated with increased seizure susceptibility

Zhang, Guojun; Raol, Yogendra Sinh H.; Hsu, Fu‐Chun; Brooks‐Kayal, Amy R.

doi:10.1046/j.1471-4159.2003.02124.x

Cited by 104 publications

(72 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In an overlapping perinatal period, decreases in GluR2 were also associated with enhanced epileptogenesis but not cell death after hypoxia-induced seizures [Sanchez et al, 2001]. Finally, long-term decreases in both GluR1 and GluR2 subunits were observed in adulthood without cell loss after 3 [Valotta da Silva et al, 2005] or after only 1 episode of status epilepticus had been induced in the neonatal period [Zhang et al, 2004]. These animals also had an increased susceptibility to KAinduced seizures.…”

Section: Discussionmentioning

confidence: 94%

Maturational Effects of Single and Multiple Early-Life Seizures on AMPA Receptors in Prepubescent Hippocampus

Friedman

Avallone²,

Magrys

2007

Dev Neurosci

View full text Add to dashboard Cite

The effects of single versus multiple episodes of status epilepticus on the expression of AMPA receptors during a critical growth spurt are unknown. To determine whether the pattern of hippocampal AMPA receptor subunit expression depends upon the age of the animal, timing and number of perinatal seizures, we characterized maturational changes in AMPA receptor protein levels of the hippocampus with immunohistochemistry and Western blotting in rats of juvenile ages with and without a history of neonatal seizures. Kainic acid (KA) was used to induce a single episode of status epilepticus (1 × KA) in rats on P20 or P30. Animals with a history of multiple seizures (3 × KA) were given KA on P6, P9, and then on P20 or P30. After 1 × KA, in P20 and P30 rats that are preferentially sensitive to CA1 damage, GluR1 immunoreactivity was depleted remarkably in CA1 stratum pyramidale and stratum lucidum and only morphologically healthy cells were faintly labeled. At P30, GluR2 subunit expression was nearly absent in the healthy cells and increased within the injured CA1 neuronal population. Western blot analysis confirmed that the GluR1/GluR2 ratio was decreased at P20 and further decreased at P30. A history of perinatal seizures (3 × KA) prevented the age-dependent alterations in the CA1. Except for areas of cell loss, NR1 and NR2A/B antibody labeling was relatively stable throughout the hippocampus at both ages and conditions examined. Data suggest that (i) Ca²⁺ permeable AMPA receptors may not be responsible for neuronal injury or irreversible cell loss and that (ii) the expression of AMPA receptors after status epilepticus depends upon the age of the animal, the timing of the first insult and subsequent formation of AMPA receptor subunit compositions within specific populations of hippocampal neurons.

show abstract

Section: Discussionmentioning

confidence: 94%

Maturational Effects of Single and Multiple Early-Life Seizures on AMPA Receptors in Prepubescent Hippocampus

Friedman

Avallone²,

Magrys

2007

Dev Neurosci

View full text Add to dashboard Cite

show abstract

“…Li-Pilo-induced SE at P10 rat does not lead to the development of SRS in adulthood (35,38). However, 25, 50, and 92% of rats developed SRS after Li-Pilo-induced SE at P12, P25, and P28, respectively (35,39).…”

Section: Discussionmentioning

confidence: 99%

Epileptogenesis Is Increased in Rats With Neonatal Isolation and Early-Life Seizure and Ameliorated by MK-801: A Long-Term MRI and Histological Study

et al. 2009

View full text Add to dashboard Cite

Early-life stress has been shown to destabilize the homeostatic synaptic plasticity and compromise the developing brain to the later encountered insults. This study would determine the long-term epileptogenic effect of neonatal isolation (NI) on early-life seizure. There were five groups: normal rearing (NR) rats; NI rats; NR rats suffering from status epilepticus (SE) at P12 (NR-SE); NI-SE rats; NI-SE-MK801 rats. All adult rats were video monitored to detect behavioral seizures, examined with brain magnetic resonance imaging, and assessed for hippocampal NeuN-immunoreactive (NeuN-IR) cells. Behavioral seizures were detected in one of six NR-SE rats, all the NI-SE rats (eight of eight), and none in the NR, NI, or NI-SE-MK801 rats. High hippocampal T2 signal were only found in three of five NR-SE rats, five of six NI-SE rats, and one of five NI-SE-MK801 rats. There was a significant decrease in the number of hippocampal NeuN-IR cells in the NR-SE and NI-SE groups, compared with the NR group, and MK-801 treatment ameliorated the neuronal loss. Our results demonstrated that NI led to an increase in epileptogenesis in rat pups with early-life SE, and treatment with MK-801 could ameliorate brain injuries, indicating a critical role of N-methyl-D-aspartic acid receptor in the epileptogenic process. (Pediatr Res 66: 441-447, 2009) S eizure is one of the most common pediatric emergencies with the highest incidence in the first year of life. Animal studies have demonstrated that early-life seizures differ essentially from seizures in the adult, including the seizure behaviors, the EEG features, and their consequences. Notwithstanding the higher susceptibility to seizures, the immature brain is less vulnerable to seizure-induced injuries than the mature brain (1-5), and diverse conditions, such as the seizure severity, causes of seizure, or precipitating injuries may affect the long-term neurologic outcome (6 -9). In this regard, the circumstances under which a seizure in immature brain can cause permanent brain damage is of great interest (9,10).In most studies published to date, early-life seizures are induced in the experimental animals under normal rearing (NR) and environmental conditions. For humans, however, most early-life seizures occur in premature and sick neonates (11-13) who are hospitalized and separated from their mothers, and hence, are under stress (14,15). Emerging evidence indicates early-life stress has enduring effects on the neuroendocrine system (16,17) and destabilizes homeostatic synaptic plasticity, particularly on the hippocampal neuroplasticity (18 -22). Stress or glucocorticoids (GCs) exposure potentiates the excitotoxic effect of concurrent neurologic insults (23), for example acceleration of kindling epileptogenesis (24), and change of seizure propensity (25). We have earlier demonstrated that rat pups subjected to repetitive neonatal isolation (NI) can exacerbate cognitive deficit and anxiety-like behaviors after recurrent seizures or status epilepticus (SE) (7,9,26). However, whe...

show abstract

“…For example, physiological and behavioral stress in the neonatal period can profoundly affect the hypothalamic-pituitary-adrenal (HPA) response to noise stress and to LPS in adults (Shanks et al, 1995(Shanks et al, , 2000. This can result in altered expression of experimental arthritis (Shanks et al, 2000), altered reactivity of the hypothalamic-pituitarygonadal axis (Nilsson et al, 2002), and persistent changes in CSF neurotransmitter levels (Coplan et al, 1996;Mathew et al, 2002) and receptor phenotypes (Hsu et al, 2003;Zhang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Alterations in Neuroimmune Responses after Neonatal Exposure to Lipopolysaccharide

Boissé

Mouihate²,

Ellis³

et al. 2004

J. Neurosci.

125

119

View full text Add to dashboard Cite

Fever is an integral part of the host's defense to infection that is orchestrated by the brain. A reduced febrile response is associated with reduced survival. Consequently, we have asked if early life immune exposure will alter febrile and neurochemical responses to immune stress in adulthood. Fourteen-day-old neonatal male rats were given Escherichia coli lipopolysaccharide (LPS) that caused either fever or hypothermia depending on ambient temperature. Control rats were given pyrogen-free saline. Regardless of the presence of neonatal fever, adult animals that had been neonatally exposed to LPS displayed attenuated fevers in response to intraperitoneal LPS but unaltered responses to intraperitoneal interleukin 1␤ or intracerebroventricular prostaglandin E 2 . The characteristic reduction in activity that accompanies fever was unaltered, however, as a function of neonatal LPS exposure. Treatment of neonates with an antigenically dissimilar LPS (Salmonella enteritidis) was equally effective in reducing adult responses to E. coli LPS, indicating an alteration in the innate immune response. In adults treated as neonates with LPS, basal levels of hypothalamic cyclooxygenase 2 (COX-2), determined by semiquantitative Western blot analysis, were significantly elevated compared with controls. In addition, whereas adult controls responded to LPS with the expected induction of COX-2, adults pretreated neonatally with LPS responded to LPS with a reduction in COX-2. Thus, neonatal LPS can alter CNS-mediated inflammatory responses in adult rats.

show abstract

Long‐term alterations in glutamate receptor and transporter expression following early‐life seizures are associated with increased seizure susceptibility

Cited by 104 publications

References 54 publications

Maturational Effects of Single and Multiple Early-Life Seizures on AMPA Receptors in Prepubescent Hippocampus

Maturational Effects of Single and Multiple Early-Life Seizures on AMPA Receptors in Prepubescent Hippocampus

Epileptogenesis Is Increased in Rats With Neonatal Isolation and Early-Life Seizure and Ameliorated by MK-801: A Long-Term MRI and Histological Study

Long-Term Alterations in Neuroimmune Responses after Neonatal Exposure to Lipopolysaccharide

Contact Info

Product

Resources

About