Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain: diffusion-weighted and T2-weighted images, regional blood volume maps, and direct correlation with tissue and cell damage

The rat brain was investigated with structural and functional magnetic resonance imaging (MRI) 12 h after the arrest of pilocarpine-induced status epilepticus lasting 4 h. Histopathological data, obtained immediately after MRI analysis, were correlated with the images through careful evaluation of tissue shrinkage. Diffusion-weighted and T2-weighted imaging showed changes throughout the cerebral cortex, hippocampus, amygdala, and medial thalamus. However, only T2-weighted imaging, based on rapid acquisition relaxation-enhanced sequences, revealed in the cortex inhomogeneous hyperintensity that was highest in a band corresponding to layer V. Regional cerebral blood volume (rCBV) maps were generated using T2*-weighted gradient-echo images and an ultrasmall superparamagnetic iron oxide contrast agent. In the cortex, rCBV peaked in superficial and deep bands exhibiting a distribution complementary to the highest T2-weighted intensity. Selective rCBV increase was also documented in the hippocampus and subcortical structures. In tissue sections, alterations indicative of marked edema were found with Nissl staining in areas corresponding to the highest T2-weighted intensity. Degenerating neurons, revealed by FluoroJadeB histochemistry, were instead concentrated in tissue exhibiting hyperperfusion in rCBV maps, such as hippocampal subfields and dentate gyrus, cortical layers II/III and VI, and medial thalamus. The data indicate that:(i) T2-weighted imaging provides a sensitive tool to investigate edematous brain alterations that follow sustained seizures; (ii) rCBV maps reveal regional hyperperfusion; (iii) rCBV peaks in tissue exhibiting marked neurodegeneration, which may not be selectively revealed by structural MRI. The findings provide an interpretation of the brain response to sustained seizures revealed in vivo by different strategies of MRI analysis.

[1]  A. Gass,et al.  Acute and chronic changes of the apparent diffusion coefficient in neurological disorders—biophysical mechanisms and possible underlying histopathology , 2001, Journal of the Neurological Sciences.

[2]  M. Bentivoglio,et al.  The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes , 2001, Neuroscience.

[3]  Martin Ingvar,et al.  Cerebral Metabolic Changes During and Following Fluorothyl‐Induced Seizures in Ventilated Rats , 1985, Journal of neurochemistry.

[4]  L. Covolan,et al.  C-Fos, Jun D and HSP72 immunoreactivity, and neuronal injury following lithium-pilocarpine induced status epilepticus in immature and adult rats. , 1998, Brain research. Molecular brain research.

[5]  B. Rosen,et al.  Functional Studies of the Human Brain Using High‐speed Magnetic Resonance Imaging , 1991, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[6]  M. Ingvar,et al.  Extra- and Intracellular pH in the Brain during Seizures and in the Recovery Period following the Arrest of Seizure Activity , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  JO McNamara,et al.  Cellular and molecular basis of epilepsy , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  J. Pellock,et al.  Epidemiology of Status Epilepticus , 1995, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[9]  E. Cavalheiro,et al.  Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study , 1983, Behavioural Brain Research.

[10]  Y. Koninck,et al.  Differential progression of Dark Neuron and Fluoro-Jade labelling in the rat hippocampus following pilocarpine-induced status epilepticus , 2000, Neuroscience.

[11]  D. Fujikawa,et al.  Seizure‐Induced Neuronal Necrosis: Implications for Programmed Cell Death Mechanisms , 2000, Epilepsia.

[12]  Meldrum Bs.  First Alfred Meyer Memorial Lecture. Epileptic brain damage: a consequence and a cause of seizures , 1997 .

[13]  J. Velazquez,et al.  Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy , 2000, Neuroscience.

[14]  M Xue,et al.  Postictal Alteration of Sodium Content and Apparent Diffusion Coefficient in Epileptic Rat Brain Induced by Kainic Acid , 1996, Epilepsia.

[15]  C. J. Wall,et al.  Rapid alterations in diffusion-weighted images with anatomic correlates in a rodent model of status epilepticus. , 2000, AJNR. American journal of neuroradiology.

[16]  Martin Ingvar,et al.  Cerebral Blood Flow and Metabolic Rate during Seizures a , 1986 .

[17]  R W Guillery,et al.  Quantification without pontification: Choosing a method for counting objects in sectioned tissues , 1997, The Journal of comparative neurology.

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

[19]  J. Gore,et al.  Changes in water diffusion and relaxation properties of rat cerebrum during status epilepticus , 1993, Magnetic resonance in medicine.

[20]  O. Hornykiewicz,et al.  The role of brain edema in epileptic brain damage induced by systemic kainic acid injection , 1984, Neuroscience.

[21]  G. Baltuch,et al.  Magnetic resonance imaging and temporal lobe epilepsy , 1998, Acta neurologica Scandinavica.

[22]  S. Benbadis,et al.  Epileptic seizures and syndromes. , 2001, Neurologic clinics.

[23]  Prof. Dr. Karl Zilles.  The Cortex of the Rat , 1985, Springer Berlin Heidelberg.

[24]  C. Marescaux,et al.  Magnetic Resonance Imaging Follow‐up of Progressive Hippocampal Changes in a Mouse Model of Mesial Temporal Lobe Epilepsy , 2000, Epilepsia.

[25]  L. Covolan,et al.  Temporal profile of neuronal injury following pilocarpine or kainic acid-induced status epilepticus , 2000, Epilepsy Research.

[26]  M. Ingvar,et al.  Local blood flow and glucose consumption in the rat brain during sustained bicuculline‐induced seizures , 1983, Acta neurologica Scandinavica.

[27]  T. Pedley,et al.  Regional cerebral blood flow in the rat during prolonged seizure activity , 1980, Brain Research.

[28]  Martin Ingvar,et al.  Metabolic, Circulatory, and Structural Alterations in the Rat Brain Induced by Sustained Pentylenetetrazole Seizures , 1984, Epilepsia.

[29]  B. Thompson,et al.  Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma , 1999, Journal of magnetic resonance imaging : JMRI.

[30]  Pl Lantos,et al.  Greenfield's Neuropathology , 1985 .

[31]  A. Reggiani,et al.  Regional Cerebral Blood Volume Mapping after Ischemic Lesions , 2000, NeuroImage.

[32]  G. Paxinos.  The Rat nervous system , 1985 .

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

[34]  J Hennig,et al.  RARE imaging: A fast imaging method for clinical MR , 1986, Magnetic resonance in medicine.

[35]  R. Sankar,et al.  Pathophysiological Mechanisms of Brain Damage from Status Epilepticus , 1993, Epilepsia.

[36]  W G Bradley,et al.  MR imaging evaluation of seizures. , 2000, Radiology.

[37]  S. Morikawa,et al.  Diffusion-weighted MR in experimental sustained seizures elicited with kainic acid. , 1995, AJNR. American journal of neuroradiology.

[38]  B. Rosen,et al.  Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation , 1998, Magnetic resonance in medicine.

[39]  Mark J. West,et al.  New stereological methods for counting neurons , 1993, Neurobiology of Aging.

[40]  M. Weiner,et al.  Metabolic and pathological effects of temporal lobe epilepsy in rat brain detected by proton spectroscopy and imaging , 1997, Brain Research.