Seizure-induced neutrophil adhesion in brain capillaries leads to a decrease in postictal cerebral blood flow
Hyun-Kyoung Lim,
Sungjun Bae,
Kayoung Han,
Bok-Man Kang,
Yoonyi Jeong,
Seong-Gi Kim,
Minah Suh
Affiliations
Hyun-Kyoung Lim
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, South Korea; Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, South Korea
Sungjun Bae
Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea; IMNEWRUN Inc, N Center Bldg. A 5F, Sungkyunkwan University, Suwon 16419, South Korea
Kayoung Han
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, South Korea; Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, South Korea
Bok-Man Kang
IMNEWRUN Inc, N Center Bldg. A 5F, Sungkyunkwan University, Suwon 16419, South Korea
Yoonyi Jeong
Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, South Korea; Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea; Department of Intelligent Precision Healthcare Convergence (IPHC), Sungkyunkwan University, Suwon 16419, South Korea
Seong-Gi Kim
Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, South Korea; Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea; Department of Intelligent Precision Healthcare Convergence (IPHC), Sungkyunkwan University, Suwon 16419, South Korea
Minah Suh
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, South Korea; Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, South Korea; Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea; IMNEWRUN Inc, N Center Bldg. A 5F, Sungkyunkwan University, Suwon 16419, South Korea; Department of Intelligent Precision Healthcare Convergence (IPHC), Sungkyunkwan University, Suwon 16419, South Korea; Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Suwon 16419, South Korea; Corresponding author
Summary: Cerebral hypoperfusion has been proposed as a potential cause of postictal neurological dysfunction in epilepsy, but its underlying mechanism is still unclear. We show that a 30% reduction in postictal cerebral blood flow (CBF) has two contributing factors: the early hypoperfusion up to ∼30 min post-seizure was mainly induced by arteriolar constriction, while the hypoperfusion that persisted for over an hour was due to increased capillary stalling induced by neutrophil adhesion to brain capillaries, decreased red blood cell (RBC) flow accompanied by constriction of capillaries and venules, and elevated intercellular adhesion molecule-1 (ICAM-1) expression. Administration of antibodies against the neutrophil marker Ly6G and against LFA-1, which mediates adhesive interactions with ICAM-1, prevented neutrophil adhesion and recovered the prolonged CBF reductions to control levels. Our findings provide evidence that seizure-induced neutrophil adhesion to cerebral microvessels via ICAM-1 leads to prolonged postictal hypoperfusion, which may underlie neurological dysfunction in epilepsy.
