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Recurrent Transient Ischemic Attack Induces Neural Cytoskeleton Modification and Gliosis in an Experimental Model

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Abstract

Transient ischemic attack (TIA) presents a high risk for subsequent stroke, Alzheimer’s disease (AD), and related dementia (ADRD). However, the neuropathophysiology of TIA has been rarely studied. By evaluating recurrent TIA-induced neuropathological changes, our study aimed to explore the potential mechanisms underlying the contribution of TIA to ADRD. In the current study, we established a recurrent TIA model by three times 10-min middle cerebral artery occlusion within a week in rat. Neither permanent neurological deficit nor apoptosis was observed following recurrent TIA. No increase of AD-related biomarkers was indicated after TIA, including increase of tau hyperphosphorylation and β-site APP cleaving enzyme 1 (BACE1). Neuronal cytoskeleton modification and neuroinflammation was found at 1, 3, and 7 days after recurrent TIA, evidenced by the reduction of microtubule-associated protein 2 (MAP2), elevation of neurofilament-light chain (NFL), and increase of glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia at the TIA-affected cerebral cortex and basal ganglion. Similar NFL, GFAP and Iba1 alteration was found in the white matter of corpus callosum. In summary, the current study demonstrated that recurrent TIA may trigger neuronal cytoskeleton change, astrogliosis, and microgliosis without induction of cell death at the acute and subacute stage. Our study indicates that TIA-induced neuronal cytoskeleton modification and neuroinflammation may be involved in the vascular contribution to cognitive impairment and dementia.

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Abbreviations

AD:

Alzheimer’s disease

ADRD:

Alzheimer’s disease (AD) and related dementia

BACE1:

β-Site APP cleaving enzyme 1

BG:

Basal ganglia

CX:

Cortex

DWI:

Diffusion-weighted imaging

GFAP:

Glial fibrillary acidic protein

Iba1:

Ionized calcium binding adaptor molecule 1

ICA:

Internal carotid artery

MAP2:

Microtubule-associated protein 2

MBP:

Myelin basic protein

MCAO:

Middle cerebral artery occlusion

NFL:

Neurofilament-light chain

ROI:

Regions of interests

TIA:

Transient ischemic attack

T2WI:

T2-weighted imaging

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Funding

This work was in part supported by National Institutes of Health grant NS109583 (SY) and a grant (#RP210046) from the Cancer Prevention and Research Institute of Texas (RB).

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Authors and Affiliations

  1. Departments of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA

    Linshu Wang, Kiran Chaudhari, Ali Winters, Yuanhong Sun, Raymond Berry, Christina Tang, Shao-Hua Yang & Ran Liu

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  1. Linshu Wang
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  2. Kiran Chaudhari
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  3. Ali Winters
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  4. Yuanhong Sun
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  6. Christina Tang
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  7. Shao-Hua Yang
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  8. Ran Liu
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Contributions

LW, RL, and SY conceived and designed the experiments; LW, AW, KC, YS, and RB performed the experiments. LW analyzed the data. LW, CT, RL, and SY wrote and edited the manuscript; all the authors reviewed the manuscript before submission.

Corresponding authors

Correspondence to Shao-Hua Yang or Ran Liu.

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All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

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Wang, L., Chaudhari, K., Winters, A. et al. Recurrent Transient Ischemic Attack Induces Neural Cytoskeleton Modification and Gliosis in an Experimental Model. Transl. Stroke Res. 14, 740–751 (2023). https://doi.org/10.1007/s12975-022-01068-7

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