TY - JOUR
T1 - Recurrent Transient Ischemic Attack Induces Neural Cytoskeleton Modification and Gliosis in an Experimental Model
AU - Wang, Linshu
AU - Chaudhari, Kiran
AU - Winters, Ali
AU - Sun, Yuanhong
AU - Berry, Raymond
AU - Tang, Christina
AU - Yang, Shao Hua
AU - Liu, Ran
N1 - Funding Information:
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).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Astrogliosis
KW - Cytoskeleton
KW - Microgliosis
KW - Neuroinflammation
KW - Transient ischemic attack
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85134660637&partnerID=8YFLogxK
U2 - 10.1007/s12975-022-01068-7
DO - 10.1007/s12975-022-01068-7
M3 - Article
AN - SCOPUS:85134660637
SN - 1868-4483
JO - Translational Stroke Research
JF - Translational Stroke Research
ER -