Effects of aging and hypertension on cerebral ischemic susceptibility: Evidenced by MR diffusion–perfusion study in rat

Aging is the most significant non-modifiable risk factor and hypertension is the most significant modifiable risk factor for ischemic stroke. We used magnetic resonance imaging (MRI) to investigate the evidence of ischemic susceptibility after aging and hypertension. Four groups of rat were studied: young normotensive Wistar-Kyoto (WKY) rat, aged normotensive WKY rat, young spontaneously hypertensive rat (SHR) and aged SHR. Brain images were acquired at a 3.0T Tim-Trio MRI system. For diffusion-weighted images, apparent diffusion coefficient (ADC) was measured. Relative cerebral blood flow (CBF) was also calculated. Cerebral ischemic susceptibility was examined by using ischemic model of bilateral common carotid artery occlusion. In the MRI study of non-ischemic rat, aged SHR had significantly higher ADC (P<0.01) and significantly lower CBF (P<0.01) in the parietal cortex, but aged WKY rat had only significantly lower CBF (P<0.01) when compared with young WKY rat. The ADC/CBF ratio in the parietal cortex was significantly higher in aged SHR when compared with young WKY rat, young SHR and aged WKY rat (P<0.01, P<0.05, P<0.05, respectively) suggesting a significant diffusion-perfusion disparity in aged SHR. After bilateral common carotid artery occlusion, there was significantly larger damage in the parietal cortex of aged SHR when compared with young WKY rat, young SHR and aged WKY rat (all P<0.05), but not in the hippocampus and thalamus (P>0.05). Our study demonstrated a significantly increased ADC value and reduced CBF in the ischemia-vulnerable cortical area. This cerebral diffusion-perfusion disparity is seen mainly in aged rat and can be more evident if associated with hypertension indicating an increased susceptibility of brain tissue to ischemic injury.

[1]  R. Cohen.  Hypertension and cerebral blood flow: implications for the development of vascular cognitive impairment in the elderly. , 2007, Stroke.

[2]  B Neal,et al.  Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials , 2000, The Lancet.

[3]  Konrad Jamrozik.  Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies , 2002 .

[4]  P. Barker,et al.  Patients with Diffusion‐Perfusion Mismatch on Magnetic Resonance Imaging 48 Hours or More After Stroke Symptom Onset: Clinical and Imaging Features , 2006, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[5]  A. Uluğ,et al.  Diffusion changes in the aging human brain. , 2000, AJNR. American journal of neuroradiology.

[6]  K. Schmidt,et al.  Comparison of Ischemic Lesion Evolution in Embolic Versus Mechanical Middle Cerebral Artery Occlusion in Sprague Dawley Rats Using Diffusion and Perfusion Imaging , 2006, Stroke.

[7]  M. Fujishima,et al.  Changes in local cerebral blood flow following bilateral carotid occlusion in spontaneously hypertensive and normotensive rats. , 1981, Stroke.

[8]  F. Bari,et al.  Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases , 2007, Brain Research Reviews.

[9]  T Katsuta,et al.  Decreased local cerebral blood flow in young and aged spontaneously hypertensive rats. , 1997, Fukuoka igaku zasshi = Hukuoka acta medica.

[10]  Jeffrey F. Thompson,et al.  Increased Apparent Diffusion Coefficients on MRI Linked with Matrix Metalloproteinases and Edema in White Matter after Bilateral Carotid Artery Occlusion in Rats , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  D. Ingram,et al.  Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function , 2000, Neurobiology of Aging.

[12]  T Hindmarsh,et al.  Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique. A methodological study of the aging brain. , 2001, Acta radiologica.

[13]  G. Albers,et al.  Applications of diffusion–perfusion magnetic resonance imaging in acute ischemic stroke , 1999, Neurology.

[14]  J. Clozel,et al.  Effects of Cilazapril on the Cerebral Circulation in Spontaneously Hypertensive Rats , 1989, Hypertension.

[15]  Tsong-Hai Lee,et al.  Hypertension downregulates the expression of brain-derived neurotrophic factor in the ischemia-vulnerable hippocampal CA1 and cortical areas after carotid artery occlusion , 2006, Brain Research.

[16]  C Thomsen,et al.  Increased self‐diffusion of brain water in normal aging , 1994, Journal of magnetic resonance imaging : JMRI.

[17]  S. Ibayashi,et al.  Cerebral blood flow and brain function in hypertension. , 1995, Hypertension research : official journal of the Japanese Society of Hypertension.

[18]  M. Kawano,et al.  Apparent diffusion coefficient map based on diffusion-weighted magnetic resonance imaging is useful in diagnosing the brainstem variant of reversible posterior leukoencephalopathy syndrome with uremia , 2010, Clinical and Experimental Nephrology.

[19]  Haruyasu Yamada,et al.  Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis , 2002, Neurobiology of Aging.

[20]  S. Kuribayashi,et al.  Hypertensive encephalopathy of brain stem with minimal supratentorial involvement: a rare manifestation of hypertensive encephalopathy. , 2005, Radiation medicine.

[21]  F. Podo,et al.  Age-dependent MRI-detected lesions at early stages of transient global ischemia in rat brain , 2004, Magnetic Resonance Materials in Physics, Biology and Medicine.

[22]  Jesper L. R. Andersson,et al.  A template for spatial normalisation of MR images of the rat brain , 2003, Journal of Neuroscience Methods.

[23]  R. Pandey,et al.  Evaluation of cerebral blood flow by single-photon emission computed tomography in young Asian Indians with hypertension , 2006, Journal of Human Hypertension.

[24]  A. Pfefferbaum,et al.  Increased brain white matter diffusivity in normal adult aging: Relationship to anisotropy and partial voluming , 2003, Magnetic resonance in medicine.

[25]  Z. G. Chen,et al.  Diffusion tensor trace mapping in normal adult brain using single-shot epi technique: A methodological study of the aging brain , 2001 .

[26]  S. Gutnikov,et al.  Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study) , 2004, The Lancet.

[27]  P. Hutchins,et al.  Anesthetic effects on hemodynamics of spontaneously hypertensive and Wistar-Kyoto rats. , 1980, The American journal of physiology.

[28]  A. Sorensen,et al.  Conversion of Ischemic Brain Tissue Into Infarction Increases With Age , 2005, Stroke.

[29]  M. Kaste,et al.  Diffusion-weighted MR imaging in normal human brains in various age groups. , 2002, AJNR. American journal of neuroradiology.

[30]  Fuhai Li,et al.  Use of diffusion- and perfusion-weighted magnetic resonance imaging in drug development for ischemic stroke. , 2003, Current drug targets. CNS and neurological disorders.

[31]  D. DeLong,et al.  The effect of aging on the apparent diffusion coefficient of normal-appearing white matter. , 2000, AJR. American journal of roentgenology.

[32]  T. Hino,et al.  Reversible brainstem hypertensive encephalopathy (RBHE): Clinicoradiologic dissociation , 2008, Clinical Neurology and Neurosurgery.

[33]  Klaus Sartor,et al.  In vivo monitoring of age-related changes in rat brain using quantitative diffusion magnetic resonance imaging and magnetic resonance relaxometry , 2002, Neuroscience Letters.

[34]  M S Buchsbaum,et al.  Regional and global changes in cerebral diffusion with normal aging. , 2001, AJNR. American journal of neuroradiology.

[35]  Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study. , 2006, Life sciences.

[36]  A. Hofman,et al.  Regional Cerebral Blood Flow and Cerebrovascular Risk Factors in the Elderly Population , 1998, Neurobiology of Aging.

[37]  L. Kappelle,et al.  Longitudinal diffusion-weighted imaging in infants with hydrocephalus: decrease in tissue water diffusion after cerebrospinal fluid diversion. , 2009, Journal of neurosurgery. Pediatrics.

[38]  L. V. van Zutphen,et al.  Differences in response to anaesthetics and analgesics between inbred rat strains , 2007, Laboratory animals.

[39]  Daniel W. Jones,et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. , 2003, JAMA.

[40]  Antoni Rodríguez-Fornells,et al.  Age-related water diffusion changes in human brain: A voxel-based approach , 2007, NeuroImage.

[41]  Timothy Q. Duong,et al.  Quantitative regional cerebral blood flow MRI of animal model of attention-deficit/hyperactivity disorder , 2007, Brain Research.