Topiramate suppresses peri-infarct spreading depolarization and improves outcomes in a rat model of photothrombotic stroke
Yuhling Wang,
Shaoyu Yen,
Yen-Yu Ian Shih,
Chien-Wen Lai,
Yu-Lin Chen,
Li-Tzong Chen,
Hsi Chen,
Lun-De Liao
Affiliations
Yuhling Wang
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan; Department of Electrical Engineering, National United University, NO.2, Lien Da, Nan Shih Li, Miao-Li 36063, Taiwan
Shaoyu Yen
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan
Yen-Yu Ian Shih
Center for Animal MRI, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Chien-Wen Lai
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan
Yu-Lin Chen
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan
Li-Tzong Chen
Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City 80708, Taiwan; National Institute of Cancer Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Township, Miaoli County 350, Taiwan
Hsi Chen
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan
Lun-De Liao
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan; Corresponding author
Summary: Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat epilepsy and alleviate migraine, has the potential to reduce PID. We employed a rat model of photothrombotic ischemia that can reliably and reproducibly induce PID and developed a combined electrocorticography-laser speckle contrast imaging (ECoG-LSCI) platform to monitor neuronal activity and cerebral blood flow (CBF) simultaneously. Topiramate administration after photothrombotic ischemia did not rescue CBF but significantly restored somatosensory evoked potentials in the forelimb area of the primary somatosensory cortex. Moreover, infarct volume was investigated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Mechanistically, the levels of inflammatory markers, such as ED1 (CD68), Iba-1, and GFAP, decreased significantly after topiramate administration, as did BDNF expression, while the expression of NeuN and Bcl-2/Bax increased, which is indicative of reduced inflammation and improved neuroprotection.
