title: Improving neurovascular outcomes with bilateral forepaw stimulation in a rat photothrombotic ischemic stroke model.
abstract: Restoring perfusion to the penumbra during the hyperacute phase of ischemic stroke is a key goal of neuroprotection. Thrombolysis is currently the only approved treatment for ischemic stroke. However, its use is limited by the narrow therapeutic window and side effect of bleeding. Therefore, other interventions are desired that could potentially increase the perfusion of the penumbra. Here, we hypothesized that bilateral peripheral electrical stimulation will improve cerebral perfusion and restore cortical neurovascular response. We assess the outcomes of bilateral forepaw electrical stimulation at intensities of 2 and 4 mA, administered either unilaterally or bilaterally. We developed a combined electrocorticogram (ECoG)-functional photoacoustic microscopy (fPAM) system to evaluate the relative changes in cerebral hemodynamic function and electrophysiologic response to acute, focal stroke. The fPAM system is used for cerebral blood volume (CBV) and hemoglobin oxygen saturation ([Formula: see text]) and the ECoG for neural activity, namely somatosensory-evoked potential (SSEP), interhemispheric coherence, and alpha-delta ratio (ADR) in response to forepaw stimulation. Our results confirmed the neuroprotective effect of bilateral forepaw stimulation at 2 mA as indicated by the 82% recovery of ADR and 95% improvement in perfusion into the region of penumbra. This experimental model can be used to study other potential interventions such as therapeutic hypertension and hypercarbia.
authors.affiliation: National University of Singapore , Singapore Institute for Neurotechnology (SINAPSE), 28 Medical Drive, #05-COR, Singapore 117456, Singapore.
authors.forename: Lun-De
authors.initials: LD
authors.lastname: Liao
authors.affiliation: National University of Singapore , Singapore Institute for Neurotechnology (SINAPSE), 28 Medical Drive, #05-COR, Singapore 117456, Singapore ; National University of Singapore , Department of Biomedical Engineering, 9 Engineering Drive 1, Block EA #03-12, Singapore 117575, Singapore.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Bandla
authors.affiliation: National University of Singapore , Singapore Institute for Neurotechnology (SINAPSE), 28 Medical Drive, #05-COR, Singapore 117456, Singapore ; National Neuroscience Institute , Department of Neurosurgery, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Ling
authors.affiliation: National University of Singapore , Singapore Institute for Neurotechnology (SINAPSE), 28 Medical Drive, #05-COR, Singapore 117456, Singapore ; National University of Singapore , Department of Electrical & Computer Engineering, Block E4, Level 5, Room 45, 4 Engineering Drive 3, Singapore 117583, Singapore.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Liu
authors.affiliation: National Health Research Institutes , Institute of Biomedical Engineering and Nanomedicine, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Kuo
authors.affiliation: National Yang Ming University , Department of Biomedical Engineering, No. 155, Sec. 2, Linong St., Taipei, Taiwan 112.
authors.forename: You-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: National Neuroscience Institute , Department of Neurosurgery, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.
authors.forename: Nicolas Kk
authors.initials: NK
authors.lastname: King
authors.affiliation: Chang Gung Memorial Hospital and Chang Gung University , Department of Physical Medicine and Rehabilitation, Taoyuan 333, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Lai
authors.affiliation: Changhua Christian Hospital , Department of Emergency Medicine, 135 Nanshsiao Street, Changhua, Taiwan 500.
authors.forename: Yan-Ren
authors.initials: YR
authors.lastname: Lin
authors.affiliation: National University of Singapore , Singapore Institute for Neurotechnology (SINAPSE), 28 Medical Drive, #05-COR, Singapore 117456, Singapore ; National University of Singapore , Department of Biomedical Engineering, 9 Engineering Drive 1, Block EA #03-12, Singapore 117575, Singapore ; National University of Singapore , Department of Electrical & Computer Engineering, Block E4, Level 5, Room 45, 4 Engineering Drive 3, Singapore 117583, Singapore ; Johns Hopkins University , Department of Biomedical Engineering, Traylor 701/720 Rutland Avenue, Baltimore, Maryland 21205.
authors.forename: Nitish V
authors.initials: NV
authors.lastname: Thakor
keywords: bilateral forepaw electrical stimulation; electrocorticography; functional photoacoustic microscopy; hyperacute ischemia; latent ipsilateral pathways; neuroprotection; peri-infarct region