Gregory Holmes

Summary

Affiliation: Dartmouth Medical School
Country: USA

Publications

  1. doi Infantile spasms: a U.S. consensus report
    John M Pellock
    Division of Child Neurology, Department of Neurology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA
    Epilepsia 51:2175-89. 2010
  2. ncbi Animal model studies application to human patients
    Gregory L Holmes
    Department of Neurology, Dartmouth Medical School, One Medical Center Drive, HB 7999, Lebanon, NH 03756, USA
    Neurology 69:S28-32. 2007
  3. ncbi Postnatal concerns in children born to women with epilepsy
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH 03756, USA
    Epilepsy Behav 11:270-6. 2007
  4. ncbi Role of extracellular sialic acid in regulation of neuronal and network excitability in the rat hippocampus
    Dmytro Isaev
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    J Neurosci 27:11587-94. 2007
  5. ncbi Timing of the developmental switch in GABA(A) mediated signaling from excitation to inhibition in CA3 rat hippocampus using gramicidin perforated patch and extracellular recordings
    Roman Tyzio
    INMED INSERM U29, 163, Marseille, France
    Epilepsia 48:96-105. 2007
  6. doi EEG abnormalities as a biomarker for cognitive comorbidities in pharmacoresistant epilepsy
    Gregory L Holmes
    Department of Neurology, Neuroscience Center at Dartmouth, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03756, USA
    Epilepsia 54:60-2. 2013
  7. doi Maturation of the human brain and epilepsy
    Gregory L Holmes
    Department of Neurology, Dartmouth Medical School, Lebanon, NH, USA
    Handb Clin Neurol 107:135-43. 2012
  8. pmc Maturation of EEG oscillations in children with sodium channel mutations
    Gregory L Holmes
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH 03756, USA
    Brain Dev 34:469-77. 2012
  9. doi The long-term effects of neonatal seizures
    Gregory L Holmes
    Department of Neurology, Dartmouth Hitchcock Medical Center, Neuroscience Center at Dartmouth, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
    Clin Perinatol 36:901-14, vii-viii. 2009
  10. ncbi Tuberous sclerosis complex and epilepsy: recent developments and future challenges
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Hanover, New Hampshire, USA
    Epilepsia 48:617-30. 2007

Research Grants

Detail Information

Publications84

  1. doi Infantile spasms: a U.S. consensus report
    John M Pellock
    Division of Child Neurology, Department of Neurology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA
    Epilepsia 51:2175-89. 2010
    ..Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS...
  2. ncbi Animal model studies application to human patients
    Gregory L Holmes
    Department of Neurology, Dartmouth Medical School, One Medical Center Drive, HB 7999, Lebanon, NH 03756, USA
    Neurology 69:S28-32. 2007
    ..Animal models can be used to evaluate different combinations of AEDs before their use in humans. Initial studies have identified combinations associated with supra-additive anticonvulsant effects that may warrant further study...
  3. ncbi Postnatal concerns in children born to women with epilepsy
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH 03756, USA
    Epilepsy Behav 11:270-6. 2007
    ..Understanding the full spectrum of AED-induced effects on the developing brain will require both rigorous basic science and clinical studies...
  4. ncbi Role of extracellular sialic acid in regulation of neuronal and network excitability in the rat hippocampus
    Dmytro Isaev
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    J Neurosci 27:11587-94. 2007
    ..We propose that decreasing the amount of extracellular sialic acid residues can be a useful approach to reduce neuronal excitability and serve as a novel therapeutic approach in the treatment of seizures...
  5. ncbi Timing of the developmental switch in GABA(A) mediated signaling from excitation to inhibition in CA3 rat hippocampus using gramicidin perforated patch and extracellular recordings
    Roman Tyzio
    INMED INSERM U29, 163, Marseille, France
    Epilepsia 48:96-105. 2007
    ..We propose that excitatory GABA contributes to enhanced excitability and ictogenesis in the neonatal rat hippocampus...
  6. doi EEG abnormalities as a biomarker for cognitive comorbidities in pharmacoresistant epilepsy
    Gregory L Holmes
    Department of Neurology, Neuroscience Center at Dartmouth, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03756, USA
    Epilepsia 54:60-2. 2013
    ..Effective treatment of pharmacoresistant epilepsy needs to target not only the overt seizures but interictal electroencephalography (EEG) abnormalities as well...
  7. doi Maturation of the human brain and epilepsy
    Gregory L Holmes
    Department of Neurology, Dartmouth Medical School, Lebanon, NH, USA
    Handb Clin Neurol 107:135-43. 2012
    ..Seizures have an age-specific effect on brain development.Whereas early life seizures rarely result in cell loss, they can induce changes in synapse organization and receptor physiology...
  8. pmc Maturation of EEG oscillations in children with sodium channel mutations
    Gregory L Holmes
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH 03756, USA
    Brain Dev 34:469-77. 2012
    ..Such abnormalities in developmental progression of oscillations may play an important role in poor cognitive development in children with DS...
  9. doi The long-term effects of neonatal seizures
    Gregory L Holmes
    Department of Neurology, Dartmouth Hitchcock Medical Center, Neuroscience Center at Dartmouth, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
    Clin Perinatol 36:901-14, vii-viii. 2009
    ..Seizures in rat pups are also associated with abnormalities in firing patterns of single cells in the hippocampus. Furthermore, these anatomic and physiologic changes correlate well with behavioral dysfunction...
  10. ncbi Tuberous sclerosis complex and epilepsy: recent developments and future challenges
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Hanover, New Hampshire, USA
    Epilepsia 48:617-30. 2007
    ..Finally, we provide an updated literature review and a consensus statement from the Tuberous Sclerosis Complex Working Group for future research into the mechanisms of epilepsy in TSC...
  11. pmc What constitutes a relevant animal model of the ketogenic diet?
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Department of Neurology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Epilepsia 49:57-60. 2008
    ..Animal models will continue to be enormously important in furthering our understanding of how dietary therapy can help individuals with epilepsy...
  12. ncbi Effects of early seizures on later behavior and epileptogenicity
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Ment Retard Dev Disabil Res Rev 10:101-5. 2004
    ..These changes occur in the absence of cell loss. Although impaired cognitive function and brain changes have been well-documented following early-onset seizures, the mechanisms of seizure-induced dysfunction remain unclear...
  13. pmc The 2008 Judith Hoyer lecture: epilepsy in children: listening to mothers
    Gregory L Holmes
    Department of Neurology, Center for Neuroscience at Dartmouth, Dartmouth Medical School, Hanover, NH, USA
    Epilepsy Behav 16:193-202. 2009
    ....
  14. pmc Lamotrigine monotherapy for newly diagnosed typical absence seizures in children
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH, USA
    Epilepsy Res 82:124-32. 2008
    ..To evaluate the efficacy, tolerability, and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures...
  15. doi Commentary on Hewapathirane et al. (in vivo imaging of seizure activity in a novel developmental seizure model) seizure-induced brain damage: from tadpoles to children
    Gregory L Holmes
    Department of Neurology, Dartmouth Medical School, Hanover, New Hampshire, USA
    Exp Neurol 213:7-9. 2008
  16. ncbi Influence of brain development on status epilepticus
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03856, USA
    Epilepsia 48:19-20. 2007
  17. pmc Choosing the correct antiepileptic drugs: from animal studies to the clinic
    Gregory L Holmes
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA
    Pediatr Neurol 38:151-62. 2008
    ..As awareness of the unique features of seizures during development increases, more drug screening in the immature animal will likely occur...
  18. ncbi Models for generalized seizures
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Medical Center Drive, Lebanon, NH 03756, USA
    Suppl Clin Neurophysiol 57:415-24. 2004
    ....
  19. ncbi Effect of topiramate following recurrent and prolonged seizures during early development
    Byung Ho Cha
    Clinical Neurophysiology Laboratory, Department of Neurology, Center for Research in Pediatric Epilepsy, Harvard Medical School, Children s Hospital Boston, Hunnewell 2, 300 Longwood Avenue, Boston, MA 02115, USA
    Epilepsy Res 51:217-32. 2002
    ..In addition, long-term administration of high-dose topiramate in the normal developing rat brain does not appear to impair cognitive performance...
  20. ncbi Postictal single-cell firing patterns in the hippocampus
    Jun li Zhou
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, New Hampshire, USA
    Epilepsia 48:713-9. 2007
    ..The purpose of this study was to study single-cell firing patterns in hippocampal cells after spontaneous seizures in rats previously subjected to status epilepticus...
  21. pmc Early life seizures cause long-standing impairment of the hippocampal map
    Havisha B Karnam
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH 03756, USA
    Exp Neurol 217:378-87. 2009
    ..This study thus provides a cellular correlate for how recurrent seizures during early development lead to cognitive impairment...
  22. ncbi Effect of the postictal state on visual-spatial memory in immature rats
    Olia Boukhezra
    Department of Neurology, Harvard Medical School, Children s Hospital Boston, Boston, MA, USA
    Epilepsy Res 55:165-75. 2003
    ..This study demonstrates that duration of postictal cognitive impairment is not directly related to duration of the seizure. The neurological status of the animal is a determining factor in duration of postictal impairment...
  23. ncbi Anticonvulsant action of GABA in the high potassium-low magnesium model of ictogenesis in the neonatal rat hippocampus in vivo and in vitro
    Dmytro Isaev
    Section of Neurology, Dartmouth Medical School, Dartmouth Hitchcock Medical School, Lebanon, NH 03756, USA
    J Neurophysiol 94:2987-92. 2005
    ..Thus in the model of high-K(+)/low Mg(2+)-induced seizures both in in vivo and in vitro conditions, GABA, acting via GABA(A) receptors, has an anticonvulsant effect during the critical developmental period of enhanced excitability...
  24. ncbi Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus
    Roustem Khazipov
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire, 03756, USA
    Eur J Neurosci 19:590-600. 2004
    ..These results suggest that, in the immature hippocampus, GABA exerts dual (both excitatory and inhibitory) actions and that the excitatory component in the action of GABA may contribute to increased excitability during early development...
  25. ncbi Effect of interictal spikes on single-cell firing patterns in the hippocampus
    Jun li Zhou
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, New Hampshire, USA
    Epilepsia 48:720-31. 2007
    ..The purpose of this study was to determine the effect of IS on single-cell firing patterns in freely moving rats with a prior history of seizures...
  26. ncbi Cognitive impairment following status epilepticus and recurrent seizures during early development: support for the "two-hit hypothesis"
    Alexandra F Hoffmann
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
    Epilepsy Behav 5:873-7. 2004
    ..No histological lesions were seen in any of the four groups. This study suggests that SE renders the immature brain vulnerable to further seizure-induced injury and this enhanced vulnerability occurs very quickly after the SE...
  27. ncbi Effect of levetiracetam on visual-spatial memory following status epilepticus
    Jun li Zhou
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, NH, USA
    Epilepsy Res 73:65-74. 2007
    ..LEV treatment resulted in less histological damage in the hippocampus but had no effect on visual-spatial function or place cell physiology in either control or SE rats...
  28. pmc Effect of age on cognitive sequelae following early life seizures in rats
    Havisha B Karnam
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire 03756, United States
    Epilepsy Res 85:221-30. 2009
    ..Animal studies can provide insights into the question of whether age of seizure onset in children is a factor in cognitive outcome...
  29. ncbi Downregulation of kainate receptors in the hippocampus following repeated seizures in immature rats
    Pushpa Tandon
    Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children s Hospital, Boston, MA 02115, USA
    Brain Res Dev Brain Res 136:145-50. 2002
    ....
  30. ncbi Effect of topiramate on cognitive function and activity level following neonatal seizures
    Qian Zhao
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH, USA
    Epilepsy Behav 6:529-36. 2005
    ..These findings show that long-term treatment with topiramate after neonatal seizures changes the long-term consequences of seizures and improves cognitive function...
  31. doi Effect of topiramate on cognitive function and single units from hippocampal place cells following status epilepticus
    Tatiana Shatskikh
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH 03756, USA
    Epilepsy Behav 14:40-7. 2009
    ..Control animals treated with topiramate did not differ from saline-treated controls on any measures. Taken together, this study shows that topiramate administered following status epilepticus has modest neuroprotective effects...
  32. ncbi Memory impairment following status epilepticus in immature rats: time-course and environmental effects
    Annemarieke Rutten
    Department of Neurology, Harvard Medical School, Children s Hospital, Boston, MA 02115, USA
    Eur J Neurosci 16:501-13. 2002
    ..Although SE results in cognitive impairment within days of the seizure, housing in an enriched environment after SE has a beneficial effect on cognitive performance in rats...
  33. ncbi Impaired single cell firing and long-term potentiation parallels memory impairment following recurrent seizures
    Jun li Zhou
    Neuroscience Center at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, New Hampshire 03756, USA
    Eur J Neurosci 25:3667-77. 2007
    ....
  34. ncbi Effects of lesions of basal forebrain cholinergic neurons in newborn rats on susceptibility to seizures
    Diosely C Silveira
    Department of Neurology, Children s Hospital and Harvard Medical School, 300 Longwood Avenue, Enders 320, Boston, MA 02155, USA
    Brain Res Dev Brain Res 139:277-83. 2002
    ..c.v. injections of SAP at P7 and controls. As in adult rats, lesions of the BF cholinergic system in rat pups result in subsequent increase in seizure susceptibility...
  35. ncbi Long-term effects of status epilepticus in the immature brain are specific for age and model
    Maria Roberta Cilio
    Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children s Hospital Boston, Boston, Massachusetts, USA
    Epilepsia 44:518-28. 2003
    ..The goal of this study was to determine whether the long-term consequences of SE during development on hippocampal plasticity and cognitive function are age and model specific...
  36. pmc Long-term suppression of GABAergic activity by neonatal seizures in rat somatosensory cortex
    Elena Isaeva
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH, USA
    Epilepsy Res 87:286-9. 2009
    ..These results indicate that decreasing the inhibitory synaptic strength following neonatal seizures in neocortical neurons is not due to a postsynaptic mechanism...
  37. ncbi Diazepam terminates brief but not prolonged seizures in young, naïve rats
    Howard P Goodkin
    Department of Neurology, Children s Hospital, Boston, Massachusetts, USA
    Epilepsia 44:1109-12. 2003
    ..This relationship has not been well studied in the developing nervous system...
  38. pmc Interictal spikes in developing rats cause long-standing cognitive deficits
    Omar I Khan
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire 03756, USA
    Neurobiol Dis 39:362-71. 2010
    ..Our findings suggest that suppressing IIS may be as important as treating seizures during brain development...
  39. ncbi Selective impairment of GABAergic synaptic transmission in the flurothyl model of neonatal seizures
    Elena Isaeva
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH 03756, USA
    Eur J Neurosci 23:1559-66. 2006
    ..We suggest that the selective depression of the amplitude of GABAergic synaptic responses may contribute to the adverse neurological and behavioral consequences that occur following neonatal seizures...
  40. pmc Hippocampal interictal spikes disrupt cognition in rats
    Jonathan K Kleen
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire
    Ann Neurol 67:250-7. 2010
    ..We investigated the transient impact of focal IISs on the hippocampus, a structure crucial for learning and memory and yet highly prone to IISs in temporal lobe epilepsy (TLE)...
  41. pmc Recurrent neonatal seizures result in long-term increases in neuronal network excitability in the rat neocortex
    Elena Isaeva
    Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH 03756, USA
    Eur J Neurosci 31:1446-55. 2010
    ..Taken together, our results suggest that recurrent seizures in infancy result in a persistent enhancement of neocortical excitability...
  42. pmc Effects of breastfeeding in children of women taking antiepileptic drugs
    K J Meador
    Department of Neurology, Emory University, Woodruff Memorial Research Building, 101 Woodruff Circle, Suite 6000, Atlanta, GA 30322, USA
    Neurology 75:1954-60. 2010
    ..Animal and human studies have demonstrated that some AEDs can adversely affect the immature brain. However, no investigation has examined effects of breastfeeding during AED therapy on subsequent cognitive abilities in children...
  43. ncbi Seizure-induced memory impairment is reduced by choline supplementation before or after status epilepticus
    Gregory L Holmes
    Department of Neurology, Center for Research in Pediatric Epilepsy, Harvard Medical School, Children s Hospital, Hunnewell 2, 300 Longwood Avenue, Boston, MA 02115, USA
    Epilepsy Res 48:3-13. 2002
    ..This study demonstrates that choline supplementation prior to or following KA-induced status epilepticus can protect rats from memory deficits induced by status epilepticus...
  44. ncbi Spontaneous recurrent seizure following status epilepticus enhances dentate gyrus neurogenesis
    Byung Ho Cha
    Department of Neurology, Harvard Medical School, Children s Hospital Boston, Boston, MA, USA
    Brain Dev 26:394-7. 2004
    ..These alterations in neurogenesis may contribute to ongoing pathological changes week and months following SE...
  45. ncbi Detrimental effects of the ketogenic diet on cognitive function in rats
    Qian Zhao
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Lebanon, NH 03756, USA
    Pediatr Res 55:498-506. 2004
    ..This study raises concerns about the long-term effects of the KD on brain development...
  46. ncbi Seizure-induced changes in place cell physiology: relationship to spatial memory
    Xianzeng Liu
    Neuroscience Center at Dartmouth, Division of Neurology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    J Neurosci 23:11505-15. 2003
    ..Our findings also suggest that the defects in place cell and spatial memory after SE and acute chemically induced seizures result from different processes...
  47. ncbi Effect of food deprivation during early development on cognition and neurogenesis in the rat
    Cigdem Akman
    Department of Neurology, Columbia Presbyterian Hospital, New York, NY, USA
    Epilepsy Behav 5:446-54. 2004
    ..Our results suggest that although food deprivation during early development reduces dentate gyrus neurogenesis, the reduced neurogenesis is not a major factor in cognitive impairment after SE in FD rats...
  48. doi Effect of TTX suppression of hippocampal activity following status epilepticus
    Qian Zhao
    Neuroscience Center at Dartmouth, Department of Neurology, Dartmouth Medical School, Hanover, NH 03756, USA
    Seizure 17:637-45. 2008
    ..TTX injection in sham-SE rats caused no cell loss or mossy fiber sprouting. These results suggest that suppression of electrical activity following SE is detrimental...
  49. ncbi Synchronization of kainate-induced epileptic activity via GABAergic inhibition in the superfused rat hippocampus in vivo
    Roustem Khazipov
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    J Neurosci 23:5337-41. 2003
    ..Thus, GABAergic inhibition is instrumental in synchronizing kainate-induced epileptiform rhythmic activity in the gamma frequency band in the intact hippocampus in vivo...
  50. doi Effects of uridine on kindling
    Qian Zhao
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, NH 03756, USA
    Epilepsy Behav 13:47-51. 2008
    ..Because of its combination of low toxicity and efficacy, uridine is a possible candidate for the treatment of epilepsy...
  51. ncbi The influence of cognitive reserve on seizure-induced injury
    Cigdem Inan Akman
    Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    Epilepsy Behav 4:435-40. 2003
    ..This study demonstrates that SE adversely effects visual-spatial memory equally in both fast and slow learners and does not support the theory that cerebral reserve plays a major role in cognitive function following a cerebral insult...
  52. pmc Altered phase precession and compression of temporal sequences by place cells in epileptic rats
    Pierre Pascal Lenck-Santini
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    J Neurosci 28:5053-62. 2008
    ..We propose that the synaptic and cellular alterations observed in MTLE induce aberrant temporal coding in the hippocampus, contributing in turn to cognitive dysfunction...
  53. ncbi Can preventative antiepileptic therapy alter outcome in infants with tuberous sclerosis complex?
    Carl E Stafstrom
    Department of Neurology, University of Wisconsin, Madison, Wisconsin 53792, USA
    Epilepsia 48:1632-4. 2007
  54. ncbi Lack of cell loss following recurrent neonatal seizures
    Peter Riviello
    Department of Neurology, Harvard Medical School, Children s Hospital, Boston, MA 02115, USA
    Brain Res Dev Brain Res 135:101-4. 2002
    ..There were no differences in cell counts between the controls and rats subjected to neonatal seizures. Like the hippocampus, the neonatal pririform and parietal cortex is resistant to seizure-induced cell loss...
  55. ncbi The expression of Fos following kainic acid-induced seizures is age-dependent
    Diosely C Silveira
    Department of Neurology, Children s Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Enders 320, Boston, Massachusetts 02115, USA
    Eur J Neurosci 15:329-44. 2002
    ....
  56. ncbi Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus
    Dmytro Isaev
    Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Hippocampus 17:210-9. 2007
    ..Although shunting GABA is already efficient in the young age group, a developmental increase in the hyperpolarizing GABA(A) driving force likely contributes to the increase in the GABAergic control of seizures upon maturation...
  57. ncbi Role of interictal epileptiform abnormalities in cognitive impairment
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Hanover, NH, USA
    Epilepsy Behav 8:504-15. 2006
    ..We suggest that interictal spikes, particularly if frequent and widespread, can impair cognitive abilities, through interference with waking learning and memory, and memory consolidation during sleep...
  58. ncbi Effects of uridine in models of epileptogenesis and seizures
    Qian Zhao
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, New Hampshire, USA
    Epilepsy Res 70:73-82. 2006
    ..In the rapid kindling models, uridine had a moderate antiepileptogenic and anticonvulsant effect. These results suggest uridine may have potential to aid in the prevention and treatment of epilepsy...
  59. ncbi Lack of effect of secretin on kindling and seizures
    Qian Zhao
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, NH, USA
    Epilepsy Behav 9:46-50. 2006
    ..Thus, in the dose range used in this preliminary acute treatment study, secretin had no discernible antiepileptogenic or anticonvulsant effects. Secretin was very well tolerated in this multidose protocol...
  60. ncbi The effect of lamotrigine on the EEGs of children and adolescents with epilepsy
    Cigdem Inan Akman
    Department of Neurology, Harvard Medical School, Children s Hospital Boston, Boston, MA, USA
    Epilepsy Behav 4:420-3. 2003
    ..9%, interictal activity in 37.8%, and ictal pattern in 41.1% of the EEG recordings. Overall, LTG resulted in improvement in electrographic features which paralleled the clinical improvement...
  61. ncbi Prolonged treatment for acute symptomatic refractory status epilepticus: outcome in children
    Mustafa Sahin
    Division of Epilepsy and Clinical Neurophysiology and the Critical Care Neurology Service, Department of Neurology, Children s Hospital, Boston, MA 02115, USA
    Neurology 61:398-401. 2003
    ..The authors therefore studied the long-term outcome in previously normal children who survived prolonged HDST for acute symptomatic RSE. All have intractable epilepsy, and none returned to baseline...
  62. ncbi Clinical evidence that epilepsy is a progressive disorder with special emphasis on epilepsy syndromes that do progress
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire, USA
    Adv Neurol 97:323-31. 2006
  63. ncbi Seizure-induced damage in the developing human: relevance of experimental models
    Gregory L Holmes
    Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children s Hospital, Boston, MA 02115, USA
    Prog Brain Res 135:321-34. 2002
    ..In addition, rodent studies supply only crude measures of learning and memory. Disturbances of language or higher cortical functions such as visual or auditory processing cannot be tested in animal models...
  64. ncbi Electrical induction of spikes in the hippocampus impairs recognition capacity and spatial memory in rats
    Tatiana N Shatskikh
    Neuroscience Center at Dartmouth, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756 001, USA
    Epilepsy Behav 9:549-56. 2006
    ..The results indicate that induction of spikes in the hippocampus results in impairment of spatial reference and nonspatial object recognition memory...
  65. pmc Antiepileptic drug use in women of childbearing age
    Kimford J Meador
    Department of Neurology, Emory University, Woodruff Memorial Research Building, 101 Woodruff Circle, Suite 6000, Mail Stop 1930 001 1AN, Atlanta, GA 30322, USA
    Epilepsy Behav 15:339-43. 2009
    ..Except for the top two AED monotherapies, there were marked differences in other monotherapies and in polytherapies between U.S. and UK centers. Future investigations are needed to examine reasons for drug choice...
  66. pmc Laterality and location influence catamenial seizure expression in women with partial epilepsy
    M Quigg
    Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA
    Neurology 73:223-7. 2009
    ..The location and laterality of the epileptic lesion as well as patient age may affect periodicity...
  67. ncbi Effects of seizures on brain development: lessons from the laboratory
    Gregory L Holmes
    Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
    Pediatr Neurol 33:1-11. 2005
    ..Recent studies have demonstrated abnormalities in single cell function that parallel behavioral changes...
  68. ncbi Neonatal seizures: characteristics of EEG ictal activity in preterm and fullterm infants
    Silvia Patrizi
    Department of Neurology, Harvard Medical School, Children s Hospital Boston, Boston, MA, USA
    Brain Dev 25:427-37. 2003
    ....
  69. ncbi Infantile spasms: criteria for an animal model
    Carl E Stafstrom
    Departments of Neurology and Pediatrics, University of Wisconsin, Madison, Wisconsin 53792, USA
    Int Rev Neurobiol 49:391-411. 2002
    ..Neither of these models conforms exactly to the human analog, but each possesses intriguing similarities that provide testable hypotheses for future investigations...
  70. ncbi Maternal deprivation stress exacerbates cognitive deficits in immature rats with recurrent seizures
    Li Tung Huang
    Department of Pediatrics and Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
    Epilepsia 43:1141-8. 2002
    ..Maternal deprivation is stressful for the neonate. The aim of this study was to investigate the short- and long-term effects of maternal separation on recurrent seizures in the developing brain...
  71. ncbi Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice
    Kiyonori Miura
    Department of Obstetrics and Gynecology, Nagasaki University School of Medicine, Nagasaki, Japan
    Neurobiol Dis 9:149-59. 2002
    ..As predicted from the dependence of UBE3A-mediated ubiquitination of p53 on HPV E6 protein, our maternal-deficient mice show normal brain p53 levels...
  72. ncbi Membrane potential of CA3 hippocampal pyramidal cells during postnatal development
    Roman Tyzio
    Institut de la Neurobiologie de la Méditterranée Institute National de la Santé et de la Recherche Médicale U29, Marseille, France
    J Neurophysiol 90:2964-72. 2003
    ..Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development...
  73. doi Excitatory GABA in rodent developing neocortex in vitro
    Sylvain Rheims
    Institut de Neurobiologie de la Mediterranee, Institut National de la Sante et de la Recherche Medicale U901, Universite de la Mediterranee, route de Luminy, Marseille, France
    J Neurophysiol 100:609-19. 2008
    ..In the companion paper, we show that the excitatory GABA drives layer-specific seizures in the immature neocortex...
  74. pmc Pilocarpine seizures cause age-dependent impairment in auditory location discrimination
    John C Neill
    Children s Hospital, Boston, USA
    J Exp Anal Behav 84:357-70. 2005
    ..Status epilepticus in rat causes an age-dependent, long-term impairment in auditory discrimination. This impairment may explain one cause of impaired auditory location discrimination in humans...
  75. ncbi Effectiveness of muscimol-containing microparticles against pilocarpine-induced focal seizures
    Daniel S Kohane
    Pediatric Intensive Care Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA
    Epilepsia 43:1462-8. 2002
    ..To investigate the efficacy of in situ lipid-protein-sugar particles (LPSPs) in mitigating the epileptogenic and histologic effects of intrahippocampal pilocarpine in rats...
  76. ncbi Effect of neonatal isolation on outcome following neonatal seizures in rats--the role of corticosterone
    Ming Chi Lai
    Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan
    Epilepsy Res 68:123-36. 2006
    ..Amelioration of neurological sequelae following reduction of the SE-induced excessive rise in plasma CORT implicates CORT in the pathogenesis of NI increasing the vulnerability to seizures...
  77. ncbi Mechanisms of action for the commonly used antiepileptic drugs: relevance to antiepileptic drug-associated neurobehavioral adverse effects
    Raman Sankar
    Department of Pediatric Neurology, Room 22474 MDCC, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1752, USA
    J Child Neurol 19:S6-14. 2004
    ..Antiglutamatergic drugs have the potential to be a double-edged sword: they can interfere with consolidation of learning and memory but can also provide neuroprotection in addition to their antiseizure effects...
  78. ncbi A single episode of neonatal seizures permanently alters glutamatergic synapses
    Gregory L Holmes
    Ann Neurol 61:379-81. 2007
  79. ncbi Early motor activity drives spindle bursts in the developing somatosensory cortex
    Rustem Khazipov
    INMED, INSERM U29, Avenue de Luminy, B P 13, 13273 Marseille, France
    Nature 432:758-61. 2004
    ..We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination...
  80. ncbi Effects of nimodipine on the behavioral sequalae of experimental status epilepticus in prepubescent rats
    Mohamad A Mikati
    Department of Pediatrics, and Adult and Pediatric Epilepsy Program, Faculty of Medicine, American University of Beirut, Lebanon
    Epilepsy Behav 5:168-74. 2004
    ..The goal of this study was to investigate the potential protective effects of nimodipine (ND), a calcium channel blocker, on the acute manifestations and long-term behavioral sequalae of experimental status epilepticus (SE)...
  81. ncbi In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures
    Ilgam Khalilov
    Institut de Neurobiologie de la Mediterranee INMED INSERM U29, 163 Route de Luminy, Marseilles 13273, France
    Nat Neurosci 6:1079-85. 2003
    ..These data indicate that the excitatory actions of GABA may be a fundamental property of epileptogenic structures...
  82. doi Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus
    Roman Tyzio
    INMED INSERM U901, Universite de la Mediterranee, 163, Avenue de Luminy, 13273 Marseille, France
    Eur J Neurosci 27:2515-28. 2008
    ..Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings...
  83. ncbi Hippocampal neurons and glia in epileptic EL mice
    Michael G Drage
    Biology Department, Boston College, Chestnut Hill, MA 02467, USA
    J Neurocytol 31:681-92. 2002
    ..The EL mouse can be a useful model for evaluating neuron-glia interactions related to idiopathic epilepsy...
  84. ncbi Possible precipitation of myoclonic seizures with oxcarbazepine
    Ahmad K Kaddurah
    Hurley Center, Flint, MI, USA
    Epilepsy Behav 8:289-93. 2006
    ....

Research Grants29

  1. Neonatal Seizures and Hippocampal Neuronal Activity
    Gregory Holmes; Fiscal Year: 2005
    ..These integrated aims will provide insight into the mechanisms of seizure-induced injury in newborns and form the basis for subsequent therapeutic interventions. ..
  2. Predictors of Seizure-Induced Memory Impairment
    Gregory Holmes; Fiscal Year: 2007
    ..Taken together these studies will provide insight into the mechanisms of seizure-induced cognitive dysfunction which will be critical as we attempt to develop novel therapeutic interventions. ..
  3. Translational Neuroscience Postdoctoral Training Program
    Gregory Holmes; Fiscal Year: 2007
    ..The close relationship between the clinical and basic science faculty, the vigor of the faculty, and the academic environment at Dartmouth makes it highly likely this will be a successful program. ..
  4. EEG Abnormalities and Cognitive Impairment
    Gregory L Holmes; Fiscal Year: 2010
    ..In addition to learning much about the cognitive impairment in epilepsy, our studies will provide enormous insight into processes involved in normal encoding and consolidation of memory. ..
  5. LONG TERM EFFECTS OF SEIZURES ON THE DEVELOPING BRAIN
    Gregory Holmes; Fiscal Year: 2002
    ..Results of this study should provide additional insights into our understanding of the long- term consequences of seizures on the developing brain. ..
  6. LONG TERM EFFECTS OF SEIZURES ON THE DEVELOPING BRAIN
    Gregory Holmes; Fiscal Year: 1999
    ..Using the expertise of two laboratories it is anticipated that this proposal will provide insights into the mechanism by which recurrent seizures lead to brain damage in young children. ..
  7. LONG TERM EFFECT OF SEIZURES ON THE DEVELOPING BRAIN
    Gregory Holmes; Fiscal Year: 1993
    ..Inferences reached in this study should increase our understanding of the importance of age of onset and the mechanisms for such age-specific differences in neurological sequelae following seizures...
  8. GABA signaling in the neocortex in normal development and epilepsy
    Gregory L Holmes; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE This study should provide valuable insights into the mechanisms by which seizures occur in the developing brain and the consequences of such seizures on brain development. ..