Diffusion Magnetic Resonance Imaging Study of a Rat Hippocampal Slice Model for Acute Brain Injury

Diffusion magnetic resonance imaging (MRI) provides a surrogate marker of acute brain pathology, yet few studies have resolved the evolution of water diffusion changes during the first 8 hours after acute injury, a critical period for therapeutic intervention. To characterize this early period, this study used a 17.6-T wide-bore magnet to measure multicomponent water diffusion at high b-values (7 to 8,080 s/mm2) for rat hippocampal slices at baseline and serially for 8 hours after treatment with the calcium ionophore A23187. The mean fast diffusing water fraction (Ffast) progressively decreased for slices treated with 10-μmol/L A23187 (—20.9 ± 6.3% at 8 hours). Slices treated with 50-μmol/L A23187 had significantly reduced Ffast 80 minutes earlier than slices treated with 10-μmol/L A23187 (P < 0.05), but otherwise, the two doses had equivalent effects on the diffusion properties of tissue water. Correlative histologic analysis showed dose-related selective vulnerability of hippocampal pyramidal neurons (CA1 > CA3) to pathologic swelling induced by A23187, confirming that particular intravoxel cell populations may contribute disproportionately to water diffusion changes observed by MRI after acute brain injury. These data suggest diffusion-weighted images at high b-values and the diffusion parameter Ffast may be highly sensitive correlates of cell swelling in nervous issue after acute injury.

[1]  B. Meldrum,et al.  The threshold and neuropathology of cerebral "anoxic-ischemic" cell change. , 1973, Archives of neurology.

[2]  B. Pressman,et al.  Biological applications of ionophores. , 1976, Annual review of biochemistry.

[3]  Kenneth R. Harris,et al.  Pressure and temperature dependence of the self diffusion coefficient of water and oxygen-18 water , 1980 .

[4]  C. Cotman,et al.  Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  D. Choi.  Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage , 1988, Trends in Neurosciences.

[6]  J. Kucharczyk,et al.  Early detection of regional cerebral ischemia in cats: Comparison of diffusion‐ and T2‐weighted MRI and spectroscopy , 1990, Magnetic resonance in medicine.

[7]  M. Mattson,et al.  Evidence for calcium-reducing and excitoprotective roles for the calcium-binding protein calbindin-1328k in cultured hippocampal neurons , 1991, Neuron.

[8]  George C. Newman,et al.  Preservation of hippocampal brain slices with in vivo or in vitro hypothermia , 1992, Brain Research.

[9]  L. Hedlund,et al.  Mechanism of Detection of Acute Cerebral Ischemia in Rats by Diffusion‐Weighted Magnetic Resonance Microscopy , 1992, Stroke.

[10]  R. Ordidge,et al.  Magnetic Resonance Imaging Assessment of Evolving Focal Cerebral Ischemia Comparison With Histopathology in Rats , 1994, Stroke.

[11]  T A Gennarelli,et al.  Hippocampal pathology in fatal human head injury without high intracranial pressure. , 1994, Journal of neurotrauma.

[12]  T. J. Teyler,et al.  Preparative methods for brain slices: a discussion , 1995, Journal of Neuroscience Methods.

[13]  G. Majno,et al.  Apoptosis, oncosis, and necrosis. An overview of cell death. , 1995, The American journal of pathology.

[14]  D. Norris,et al.  Biexponential diffusion attenuation in various states of brain tissue: Implications for diffusion‐weighted imaging , 1996, Magnetic resonance in medicine.

[15]  T. Takadera,et al.  Apoptotic cell death and caspase 3 (CPP32) activation induced by calcium ionophore at low concentrations and their prevention by nerve growth factor in PC12 cells. , 1997, European journal of biochemistry.

[16]  Y. Cohen,et al.  Diffusion- and T2-weighted MRI of closed-head injury in rats: a time course study and correlation with histology. , 1997, Magnetic resonance imaging.

[17]  D L Buckley,et al.  MR microscopy of perfused brain slices , 1997, Magnetic resonance in medicine.

[18]  R M Henkelman,et al.  Water dynamics in human blood via combined measurements of T2 relaxation and diffusion in the presence of gadolinium , 1998, Magnetic resonance in medicine.

[19]  H Soltanian-Zadeh,et al.  Time course of ADCw changes in ischemic stroke: beyond the human eye! , 1998, Stroke.

[20]  J. Trojanowski,et al.  gThe Dorothy Russell Memorial Lecture* The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms , 1998, Neuropathology and applied neurobiology.

[21]  C. Beaulieu,et al.  Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: Evolution of lesion volume and correlation with clinical outcome , 1999, Annals of neurology.

[22]  D. L. Buckley,et al.  Nuclear magnetic resonance imaging measurements of water diffusion in the perfused hippocampal slice during N-methyl-d-aspartate-induced excitotoxicity , 1999, Neuroscience.

[23]  D L Buckley,et al.  The effect of ouabain on water diffusion in the rat hippocampal slice measured by high resolution NMR imaging , 1999, Magnetic resonance in medicine.

[24]  M. Jacquin,et al.  Calcium ionophores can induce either apoptosis or necrosis in cultured cortical neurons , 1999, Neuroscience.

[25]  C. Westin,et al.  Multi‐component apparent diffusion coefficients in human brain † , 1999, NMR in biomedicine.

[26]  Diffusing into the future. , 2000, AJNR. American journal of neuroradiology.

[27]  B. Mock,et al.  High-b-value diffusion-weighted MR imaging of suspected brain infarction. , 2000, AJNR. American journal of neuroradiology.

[28]  J. Grotta,et al.  Early stroke treatment associated with better outcome: the ninds rt-pa stroke study , 2000, Neurology.

[29]  O. Hansson,et al.  Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons , 2000, Brain Research.

[30]  P. Kochanek,et al.  The simple model versus the super model: translating experimental traumatic brain injury research to the bedside. , 2001, Journal of neurotrauma.

[31]  A. Faden.  Neuroprotection and traumatic brain injury: the search continues. , 2001, Archives of neurology.

[32]  S. Warach.  New imaging strategies for patient selection for thrombolytic and neuroprotective therapies , 2001, Neurology.

[33]  Stephen J Blackband,et al.  Human erythrocyte ghosts: Exploring the origins of multiexponential water diffusion in a model biological tissue with magnetic resonance , 2002, Magnetic resonance in medicine.

[34]  Timothy M. Shepherd,et al.  Simultaneous diffusion MRI measurements from multiple perfused rat hippocampal slices , 2002, Magnetic resonance in medicine.

[35]  S. Warach.  Thrombolysis in stroke beyond three hours: Targeting patients with diffusion and perfusion MRI , 2002, Annals of neurology.

[36]  S. Roper,et al.  Water diffusion measurements in perfused human hippocampal slices undergoing tonicity changes , 2003, Magnetic resonance in medicine.

[37]  Y. Olsson,et al.  The dentate gyrus in hypoglycemia: Pathology implicating excititoxin-mediated neuronal necrosis , 2004, Acta Neuropathologica.

[38]  F. Chiu,et al.  Calcium Ionophore-Induced Degradation of Neurofilament and Cell Death in MSN Neuroblastoma Cells , 1998, Neurochemical Research.

[39]  R. L. Hayes,et al.  Maitotoxin Induces Calpain But Not Caspase-3 Activation and Necrotic Cell Death in Primary Septo-Hippocampal Cultures , 1999, Neurochemical Research.

[40]  Pierre J. Magistretti,et al.  Brain energy metabolism , 2013 .