Longitudinal hippocampal volumetric changes in mice following brain infarction

Vanessa H Brait,Alexander Oman,Leigh A Johnston,Katrina R O’Brien,Warda T Syeda,Leonid Churilov,Emilio Werden,Charlotte M Ermine,Lachlan H Thompson,Jess Nithianantharajah,Mohsen Nategh,David K Wright,Katherine A Jackman,Amy Brodtmann

doi:10.1038/s41598-021-88284-7

Abstract

Hippocampal atrophy is increasingly described in many neurodegenerative syndromes in humans, including stroke and vascular cognitive impairment. However, the progression of brain volume changes after stroke in rodent models is poorly characterized. We aimed to monitor hippocampal atrophy occurring in mice up to 48-weeks post-stroke. Male C57BL/6J mice were subjected to an intraluminal filament-induced middle cerebral artery occlusion (MCAO). At baseline, 3-days, and 1-, 4-, 12-, 24-, 36- and 48-weeks post-surgery, we measured sensorimotor behavior and hippocampal volumes from T2-weighted MRI scans. Hippocampal volume—both ipsilateral and contralateral—increased over the life-span of sham-operated mice. In MCAO-subjected mice, different trajectories of ipsilateral hippocampal volume change were observed dependent on whether the hippocampus contained direct infarction, with a decrease in directly infarcted tissue and an increase in non-infarcted tissue. To further investigate these volume changes, neuronal and glial cell densities were assessed in histological brain sections from the subset of MCAO mice lacking hippocampal infarction. Our findings demonstrate previously uncharacterized changes in hippocampal volume and potentially brain parenchymal cell density up to 48-weeks in both sham- and MCAO-operated mice.

Highlights

Been described[26,27], the longitudinal trajectory of microglial and astrocytic proliferation and the subsequent pathophysiological secondary neurodegeneration (SND) response to stroke remains poorly understood
We hypothesized that in sham-operated mice hippocampal volume would increase initially due to normal growth, but remain stable in adulthood, and that ipsilesional hippocampal atrophy would occur post-stroke, regardless of whether the hippocampus was directly infarcted
During the 30-min ischemic period, regional cerebral blood flow (rCBF) was maintained at an average of 12% of the preischemic baseline, and after filament removal, it returned to baseline (Fig. 1a)

Summary

Introduction

Been described[26,27], the longitudinal trajectory of microglial and astrocytic proliferation and the subsequent pathophysiological SND response to stroke remains poorly understood. Whilst brain atrophy is an almost universal part of normal aging[28,29], it may be related to human life-style risk factors[8] and may not occur in rodents. It is necessary to first understand and depict the brain trajectories of normal rodent aging to establish a baseline that enables more rational interpretation of possible stroke-related changes. We aimed to examine the volume of the hippocampus up to 48-weeks post-MCAO in wild-type mice, using sham-operated mice as their controls. We hypothesized that in sham-operated mice hippocampal volume would increase initially due to normal growth, but remain stable in adulthood, and that ipsilesional hippocampal atrophy would occur post-stroke, regardless of whether the hippocampus was directly infarcted

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Discussion

Conclusion