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. 2023 Dec;167(6):733-752.
doi: 10.1111/jnc.16008. Epub 2023 Nov 27.

Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke

Rebecca J Hood  1   2   3 , Sonia Sanchez-Bezanilla  2   3 , Daniel J Beard  2   3 , Ruslan Rust  4   5 , Renée J Turner  1 , Shannon M Stuckey  1 , Lyndsey E Collins-Praino  1 , Frederick R Walker  2   3   6 , Michael Nilsson  3   6   7   8 , Lin Kooi Ong  2   3   9   10
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Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke

Rebecca J Hood et al. J Neurochem. 2023 Dec.

Abstract

We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid-β accumulation in the hippocampus, a region remote from the primary infarct. Interestingly, there is emerging evidence suggesting that deposition of amyloid-β around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood-brain barrier integrity. However, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the current study, we aimed to characterise the spatiotemporal cerebrovascular changes after cortical stroke. This was done using the photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Cerebrovascular morphology as well as the co-localisation of amyloid-β with vasculature and blood-brain barrier integrity were assessed in the cortex and hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed transient cerebrovascular remodelling in the peri-infarct area up to 28 days post-stroke. Importantly, the cerebrovascular changes were extended beyond the peri-infarct region to the ipsilateral hippocampus and were sustained out to 84 days post-stroke. When investigating vessel diameter, we showed a decrease at 84 days in the peri-infarct and CA1 regions that were exacerbated in vessels with amyloid-β deposition. Lastly, we showed sustained vascular leakage in the peri-infarct and ipsilateral hippocampus, indicative of a compromised blood-brain-barrier. Our findings indicate that hippocampal vasculature may represent an important therapeutic target to mitigate the progression of post-stroke cognitive impairment.

Keywords: amyloid-β; blood-brain barrier; cerebrovascular; secondary neurodegeneration; stroke.

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References

REFERENCES

    1. Abe, O., Nakane, M., Aoki, S., Hayashi, N., Masumoto, T., Kunimatsu, A., Mori, H., Tamura, A., & Ohtomo, K. (2003). MR imaging of postischemic neuronal death in the substantia nigra and thalamus following middle cerebral artery occlusion in rats. NMR in Biomedicine, 16(3), 152-159.
    1. Attwell, D., Buchan, A. M., Charpak, S., Lauritzen, M., Macvicar, B. A., & Newman, E. A. (2010). Glial and neuronal control of brain blood flow. Nature, 468(7321), 232-243.
    1. Barba, R., Martinez-Espinosa, S., Rodriguez-Garcia, E., Pondal, M., Vivancos, J., & Del Ser, T. (2000). Poststroke dementia: Clinical features and risk factors. Stroke, 31(7), 1494-1501.
    1. Baron, J. C., Yamauchi, H., Fujioka, M., & Endres, M. (2014). Selective neuronal loss in ischemic stroke and cerebrovascular disease. Journal of Cerebral Blood Flow and Metabolism, 34(1), 2-18.
    1. Bernardo-Castro, S., Sousa, J. A., Bras, A., Cecilia, C., Rodrigues, B., Almendra, L., et al. (2020). Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery. Frontiers in Neurology, 11, 594672.

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