Improving neurovascular outcomes with bilateral forepaw stimulation in a rat photothrombotic ischemic stroke model

Lun De Liao*, Aishwarya Bandla, Ji Min Ling, Yu Hang Liu, Li Wei Kuo, You Yin Chen, Nicolas Kk King, Hsin Yi Lai, Yan Ren Lin, Nitish V. Thakor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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 (SO2) 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.

Original languageEnglish
Article number011007
Issue number1
StatePublished - 1 Jul 2014


  • bilateral forepaw electrical stimulation
  • electrocorticography
  • functional photoacoustic microscopy
  • hyperacute ischemia
  • latent ipsilateral pathways
  • neuroprotection
  • peri-infarct region


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