Hippocampal atrophy and abnormal brain development following a prolonged hyperthermic seizure in the immature rat with a focal neocortical lesion

In rats subjected to a focal cortical lesion soon after birth, hyperthermia at P10 induces a prolonged epileptic seizure, often followed by temporal lobe epilepsy in the adult. To determine whether brain damage and notably hippocampal atrophy occur early on in this model, whole brain as well as hemispheric, cortical, subcortical and hippocampal volumes was measured in non-lesioned and lesioned rat pups, 2 days (P12) and 12 days (P22) after the hyperthermic seizure. All pups with a cortical lesion showed reductions in whole brain and in ipsilateral hemispheric, cortical and hippocampal volumes at P12, which persisted at P22 in pups having also sustained a prolonged hyperthermic seizure at P10. Limiting the duration of the seizure with Diazepam prevented the hippocampal atrophy. Thus, a prolonged hyperthermic seizure in immature brain with a subtle neocortical lesion impairs normal brain development, and the duration of the seizure appears to be a key factor in generating hippocampal atrophy.

[1]  S. Moshé,et al.  Neuronal Migration Disorders Increase Susceptibility to Hyperthermia‐Induced Seizures in Developing Rats , 1996, Epilepsia.

[2]  P. Camfield Recurrent Seizures in the Developing Brain Are Not Harmful , 1997, Epilepsia.

[3]  T. Baram,et al.  Febrile seizures: an appropriate-aged model suitable for long-term studies. , 1997, Brain research. Developmental brain research.

[4]  Z. Bortolotto,et al.  The susceptibility of rats to pilocarpine-induced seizures is age-dependent. , 1987, Brain research.

[5]  J. Cavazos,et al.  Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions , 1998, Annals of neurology.

[6]  J. Ellenberg,et al.  Predictors of epilepsy in children who have experienced febrile seizures. , 1976, The New England journal of medicine.

[7]  E. Syková,et al.  Diffusion properties of the brain in health and disease , 2004, Neurochemistry International.

[8]  N. Lanerolle,et al.  The Neuropathology of Hyperthermic Seizures in the Rat , 1999, Epilepsia.

[9]  G. Rásonyi,et al.  Hippocampal malrotation with normal corpus callosum: a new entity? , 2000, Neuroradiology.

[10]  J. Swann,et al.  Spine loss and other dendritic abnormalities in epilepsy , 2000, Hippocampus.

[11]  Pablo Lema,et al.  Febrile seizures in the predisposed brain: A new model of temporal lobe epilepsy , 2005, Annals of neurology.

[12]  P. Schauwecker Genetic basis of kainate-induced excitotoxicity in mice: phenotypic modulation of seizure-induced cell death , 2003, Epilepsy Research.

[13]  L. Carmant,et al.  The pathological basis of temporal lobe epilepsy in childhood , 2003, Neurology.

[14]  J. Velíšková,et al.  Susceptibility of immature and adult brains to seizure effects , 2004, The Lancet Neurology.

[15]  C. Wasterlain,et al.  Electroconvulsive seizures in the immature rat adversely affect myelin accumulation , 1982, Experimental Neurology.

[16]  K. Dvořák,et al.  Experimentally induced focal microgyria and status verrucosus deformis in rats — Pathogenesis and interrelation histological and autoradiographical study , 1978, Acta Neuropathologica.

[17]  L. Carmant,et al.  Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy , 2004, Neurology.

[18]  C. Wasterlain Effects of neonatal status epilepticus on rat brain development , 1976, Neurology.

[19]  Prognosis Guidelines for Epidemiologic Studies on Epilepsy , 1993, Epilepsia.

[20]  C. Wasterlain Recurrent Seizures in the Developing Brain Are Harmful , 1997, Epilepsia.

[21]  B. Litt,et al.  Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. , 2006, Brain : a journal of neurology.

[22]  Jacqueline A. French,et al.  Characteristics of medial temporal lobe epilepsy , 1993 .

[23]  Y. Ben‐Ari,et al.  Kainic acid seizure syndrome and binding sites in developing rats. , 1984, Brain research.

[24]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[25]  Amy L. Brewster,et al.  Fever, febrile seizures and epilepsy , 2007, Trends in Neurosciences.

[26]  F Andermann,et al.  Analysis of shape and positioning of the hippocampal formation: an MRI study in patients with partial epilepsy and healthy controls. , 2005, Brain : a journal of neurology.

[27]  F. Knudsen Febrile seizures — treatment and outcome , 1996, Brain and Development.

[28]  F Cendes,et al.  Frequency and characteristics of dual pathology in patients with lesional epilepsy , 1995, Neurology.

[29]  L. Schmued,et al.  Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration , 2000, Brain Research.

[30]  P. Gloor,et al.  Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy , 1993, Neurology.

[31]  W. Löscher,et al.  Delayed Sclerosis, Neuroprotection, and Limbic Epileptogenesis After Status Epilepticus in the Rat , 2002, Epilepsia.

[32]  Chao-Ching Huang,et al.  Febrile seizures impair memory and cAMP response‐element binding protein activation , 2003, Annals of neurology.

[33]  W. Scherle,et al.  A simple method for volumetry of organs in quantitative stereology. , 1970, Mikroskopie.

[34]  William H Theodore,et al.  Total cerebral volume is reduced in patients with localization-related epilepsy and a history of complex febrile seizures. , 2003, Archives of neurology.

[35]  P. Timiras,et al.  A Stereotaxic Atlas of the Developing Rat Brain , 1970 .

[36]  Lionel Carmant,et al.  Freeze Lesion–Induced Focal Cortical Dysplasia Predisposes to Atypical Hyperthermic Seizures in the Immature Rat , 2004, Epilepsia.

[37]  P. Stanton,et al.  Flurothyl status epilepticus in developing rats: behavioral, electrographic histological and electrophysiological studies. , 1999, Brain research. Developmental brain research.

[38]  A. Peiffer,et al.  Brain weight differences associated with induced focal microgyria , 2003, BMC Neuroscience.

[39]  M. Gruenthal Electroencephalographic and histological characteristics of a model of limbic status epilepticus permitting direct control over seizure duration , 1998, Epilepsy Research.

[40]  G. SadleirLynette,et al.  Febrile seizures , 2007 .

[41]  F Andermann,et al.  Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes , 2001, Neurology.

[42]  A. Galaburda,et al.  Changes in efferent and afferent connectivity in rats with induced cerebrocortical microgyria , 2000, The Journal of comparative neurology.

[43]  Orhan Nalcioglu,et al.  Serial MRI after experimental febrile seizures: Altered T2 signal without neuronal death , 2004, Annals of neurology.

[44]  J. Engel Mesial Temporal Lobe Epilepsy: What Have We Learned? , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[45]  T. Baram,et al.  Seizure-Induced Neuronal Injury: Vulnerability to Febrile Seizures in an Immature Rat Model , 1998, The Journal of Neuroscience.

[46]  D. Spencer,et al.  Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination , 1993, Annals of neurology.

[47]  Glenn D. Rosen,et al.  Brain volume estimation from serial section measurements: a comparison of methodologies , 1990, Journal of Neuroscience Methods.

[48]  D. Arnold,et al.  Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region. , 2003, Brain : a journal of neurology.

[49]  O W Witte,et al.  Differential Downregulation of GABAA Receptor Subunits in Widespread Brain Regions in the Freeze-Lesion Model of Focal Cortical Malformations , 2000, The Journal of Neuroscience.

[50]  A. Nehlig,et al.  Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats , 2002, Epilepsia.

[51]  S. Shorvon,et al.  Association of hippocampal sclerosis with cortical dysgenesis in patients with epilepsy , 1994, Neurology.

[52]  R. Sankar,et al.  Seizure-induced neuronal death in the immature brain. , 2002, Progress in brain research.

[53]  T. Babb,et al.  Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: the problem of dual pathology. , 1991, Journal of neurosurgery.

[54]  T. Babb,et al.  The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. , 1995, Brain : a journal of neurology.

[55]  A. Cole,et al.  Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood , 1999, Neurology.

[56]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[57]  Peter R. Mouton,et al.  Principles and Practices of Unbiased Stereology: An Introduction for Bioscientists , 2002 .