An MRI-histological study of white matter in stroke-free SHRSP

Abstract

Hypertension is associated with cerebral small vessel disease (SVD) and with diffuse white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI). We tested whether stroke-prone spontaneously hypertensive rats (SHRSP), a model of chronic hypertension, exhibit WMH. Male SHRSP (age 10 months) without stroke symptoms were compared with age-matched male WKY rats. Stroke-prone spontaneously hypertensive rats exhibited no WMH on MRI scans (T2, T2*, diffusion tensor imaging) and no neuropathological lesions. While leptomeningeal arteries exhibited fibrohyaline wall thickening, with decreased smooth muscle actin relative to WKY, deep penetrating arterioles within the caudate nuclei had no vasculopathy. We conclude that WMH are not an obligate feature of stroke-free SHRSP aged up to 10 months.

Figure 1

Magnetic resonance imaging (MRI) scans of stroke-free stroke-prone spontaneously hypertensive rats (SHRSP) brain. MRI scans (coronal section) from a representative male SHRSP aged 48 weeks. T₂-weighted (A), gradient-echo T₂*-weighted (B) and color-coded fractional anisotropy map (C). The color ball in (C) indicates the three directional vectors (red–blue–green). Scans show no white matter hyperintensities (WMH) (A), no significant hemorrhage (B) and no loss of white matter anisotropy (C).

Figure 2

Histological examination of white matter. Immunohistochemical labeling of myelin basic protein (MBP) in brain sections from a representative stroke-prone spontaneously hypertensive rat (SHRSP), aged 47 weeks. (A) MBP immunolabeling (brown) displays histological white matter areas in low magnification view of a coronal section. The corpus callosum (cc) and caudate (caud) are marked. (B) A neighboring section treated identically but without primary antibody shows no immunoreactivity. (C, D) Higher magnification images confirm integrity of myelin in corpus callosal white matter (C) and in caudate white matter bundles (D). The central azimuthal artery serves as an anatomical landmark in (C). Nuclear chromatin is counterstained with hematoxylin (blue). Scale bars: 1,000 μm (A, B) and 20 μm (C, D).