T2‐Weighted MRI Correlates with Long‐Term Histopathology, Neurology Scores, and Skilled Motor Behavior in a Rat Stroke Model

Abstract: The intraluminal suture model of transient middle cerebral artery occlusion (MCAO) in the Sprague Dawley strain of rats characteristically results in an inconsistently sized brain lesion. The purpose of the investigation reported here was to determine whether there were strong point‐to‐point correlations between the degree of cortical lesion size, as assessed in vivo using T2‐weighted magnetic resonance imaging (MRI) and corresponding cortical lesion size using routine histopathological techniques. Moreover, we aimed to investigate if cortical lesion size as determined by these two modalities correlates with neurological and/or skilled motor deficits observed in individual animals. Baseline behavioral scores were obtained on the animals prior to receiving 60 min of transient MCAO. Following MCAO, animals were tested for 1–21 days for neurological deficits. T2‐weighted MRIs of the cortex were taken at two and seven days post‐MCAO. At 30 and 60 days the rats were retested for forelimb dexterity in the staircase test. Subsequently, the cortex was examined for histopathological damage. Indeed, there were highly significant correlations between lesion size determined by MRI and histopathology. The degree of cortical damage observed in the T2‐weighted MRI, as well as the size of the histopathological lesions were, in turn, highly correlated with the degrees of deficiencies observed in the composite neurological assessments and with the deficits involving skilled use of the contralateral forepaw (damaged side).

[1]  D. Corbett,et al.  Long-Term Functional End Points Following Middle Cerebral Artery Occlusion in the Rat , 2000, Pharmacology Biochemistry and Behavior.

[2]  G. Sutherland,et al.  AR-R15896AR reduces cerebral infarction volumes after focal ischemia in cats. , 2000, Neurosurgery.

[3]  P M Matthews,et al.  Relating MRI changes to motor deficit after ischemic stroke by segmentation of functional motor pathways. , 2000, Stroke.

[4]  J. L. Raszkiewicz,et al.  NPS 1506, A Novel NMDA Receptor Antagonist and Neuroprotectant: Review of Preclinical and Clinical Studies , 1999, Annals of the New York Academy of Sciences.

[5]  S. Sydserff,et al.  Efficacy of AR-R15896AR in the rat monofilament model of transient middle cerebral artery occlusion. , 1999, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[6]  R. Ridley,et al.  Functional Benefit from Clomethiazole Treatment after Focal Cerebral Ischemia in a Nonhuman Primate Species , 1999, Experimental Neurology.

[7]  A. Buchan,et al.  Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. , 1999, Stroke.

[8]  D. Corbett,et al.  -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. , 1997, The Journal of pharmacology and experimental therapeutics.

[9]  S. Warach,et al.  Pitfalls and potential of clinical diffusion-weighted MR imaging in acute stroke. , 1997, Stroke.

[10]  Michael Chopp,et al.  The temporal evolution of MRI tissue signatures after transient middle cerebral artery occlusion in rat , 1997, Journal of the Neurological Sciences.

[11]  J. Grotta,et al.  Combined neuroprotection and reperfusion therapy for stroke. Effect of lubeluzole and diaspirin cross-linked hemoglobin in experimental focal ischemia. , 1996, Stroke.

[12]  Reduction of excitotoxicity-induced brain damage by the competitive NMDA antagonist CGP 40116: a longitudinal study using diffusion-weighted imaging , 1996, Neuroscience Letters.

[13]  D. Corbett,et al.  Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  D. Saunders,et al.  Measurement of infarct size using MRI predicts prognosis in middle cerebral artery infarction. , 1995, Stroke.

[15]  R. Busto,et al.  HU-211, a novel noncompetitive N-methyl-D-aspartate antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat. , 1995, Stroke.

[16]  G. Steinberg,et al.  Correlation of CGS 19755 Neuroprotection against in vitro Excitotoxicity and Focal Cerebral Ischemia , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  A. Tamura,et al.  The Neuroprotective Effect of the Novel Noncompetitive NMDA Antagonist, FR115427 in Focal Cerebral Ischemia in Rats , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

[19]  B. Johansson,et al.  Paw‐Reaching, Sensorimotor, and Rotational Behavior After Brain Infarction in Rats , 1993, Stroke.

[20]  C. Sotak,et al.  Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion‐weighted MRI , 1993, Neurology.

[21]  B. Siesjö Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. , 1992, Journal of neurosurgery.

[22]  B. Volpe,et al.  Pharmacological Effects of Remacemide and MK-801 on Memory and Hippocampal CA1 Damage in the Rat Four-Vessel Occlusion (4-VO) Model of Global Ischemia , 1992 .

[23]  P. Weinstein,et al.  Reversible middle cerebral artery occlusion without craniectomy in rats. , 1989, Stroke.