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Updated: May 14, 2026
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
An MRI-histological study of white matter in stroke-free SHRSP
John F Brittain1, Christopher McCabe, Halima Khatun
1Stroke and Dementia Research Centre, St Georges University of London, London, UK.
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.
Insights
Stroke-prone spontaneously hypertensive rats (SHRSP) do not show white matter hyperintensities (WMH) or neuropathological lesions, even with hypertension. These findings suggest WMH are not an inevitable outcome of chronic hypertension in this rat model.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Medical Imaging
Background:
- Hypertension is linked to cerebral small vessel disease (SVD) and white matter hyperintensities (WMH) seen on MRI.
- Stroke-prone spontaneously hypertensive rats (SHRSP) are a common model for studying chronic hypertension.
Purpose of the Study:
- To investigate whether SHRSP exhibit WMH, a common feature in hypertensive humans.
- To determine if WMH are an obligate consequence of chronic hypertension in this animal model.
Main Methods:
- Comparison of 10-month-old male SHRSP without stroke symptoms to age-matched WKY rats.
- Magnetic resonance imaging (MRI) including T2, T2*, and diffusion tensor imaging (DTI).
- Neuropathological examination of brain tissue.
Main Results:
- SHRSP showed no evidence of WMH on any MRI sequences.
- No significant neuropathological lesions were observed in SHRSP.
- Leptomeningeal arteries in SHRSP displayed fibrohyaline wall thickening and reduced smooth muscle actin compared to WKY rats.
- Deep penetrating arterioles in the caudate nuclei of SHRSP did not show vasculopathy.
Conclusions:
- WMH are not a mandatory feature in stroke-free SHRSP up to 10 months of age.
- The absence of WMH in this model suggests hypertension alone may not directly cause WMH without other contributing factors.
- Further research is needed to understand the specific mechanisms leading to WMH in human hypertension.
