Neurovascular function recovery after focal ischemic stroke by enhancing cerebral collateral circulation via peripheral stimulation-mediated interarterial anastomosis

Abstract

Current treatments for ischemic stroke have focused on the administration of a tissue plasminogen activator, although the associated side effects and subsequent reperfusion injury remain challenging. Peripheral electrical stimulation has shed light on therapeutic interventions for ischemia by increasing cerebral blood flow (CBF) to the target region through collateral circulation, although the mechanism remains elusive. Here, a focal photothrombotic ischemic (PTI) stroke was induced in the right hemispheric primary somatosensory forelimb cortex (S1FL) of rat brains, and the therapeutic effects of forelimb and hindlimb stimulation were characterized at the contralesional S1FL. We observed that PTI stroke rats that received forelimb stimulation exhibited significantly restored CBF of the ischemic penumbra ([Formula: see text] for the S1FL and [Formula: see text] for the primary somatosensory hindlimb cortex, respectively), electrocorticography (ECoG) delta band coherence of the intercortical S1FL ([Formula: see text]) at the 75th min poststroke and an ischemic infarct ([Formula: see text]) via collateral circulation recruitment. Importantly, anterior cerebral artery/middle cerebral artery (ACA-MCA) interarterial anastomotic regulation occurred upon forelimb stimulation and played roles in the recovery of neurovascular functions. These results indicated that receptive field-specific stimulation further restores CBF, neuronal activities, and tissue viability through the enhancement of ACA-MCA interarterial anastomosis-mediated collateral circulation and provides a feasible therapeutic intervention for stroke recovery.

Spatiotemporal dynamics of pial collateral blood flow following permanent middle cerebral artery occlusion in a rat model of sensory-based protection: a Doppler optical coherence tomography study

“…Such activation results in functional and structural protection from impending ischemic stroke, findings that were independently replicated in other labs. [5][6][7][8][9][10] Further, our findings [11][12][13][14][15][16][17][18] (reviewed in Refs. [19][20][21] have demonstrated that such stimulus-based protection is achievable in anesthetized rats, unrestrained behaving rats, and in old rats.…”

Sensory stimulation-based protection from impending stroke following MCA occlusion is correlated with desynchronization of widespread spontaneous local field potentials

“…We have used a rat model of cerebral ischemia, a dorsal permanent Middle Cerebral Artery occlusion (pMCAo) that results in cortical infarct and functional deficits 24 h after ischemic onset as assessed by functional imaging, blood flow imaging, neuronal recordings, and histological staining, in addition to behavioral impairments assessed one-week post occlusion 2 . However, applying the same assessment techniques we have demonstrated that intermittent sensory (whisker) stimulation delivered during the hyperacute state post pMCAo as an ‘early’ treatment immediately after pMCAo (+0 h), 1 h or 2 h after pMCAo (+1 h and +2 h respectively) protects the cortex from ischemic stroke damage (see similar findings 3 , 4 ). Beyond the 2 h early protection window, the same sensory stimulation treatment is not protective anymore and could even exacerbate damage if delivered as ‘late’ treatment 3 h (+3 h) after ischemic onset (reviewed in 5 ).…”

Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke

“…The skin of the scalp was removed from the skull to expose the bregma and the lambda as reference points. The location of the window was at the intersection of the middle cerebral artery (MCA) and anterior cerebral artery, which is associated with primary somatosensory cortex forelimb region (S1FL) and the primary somatosensory cortex hindlimb region (S1HL; anterior/posterior: -1 mm and medial/lateral: 1.5 mm; anterior/posterior: 3 mm; and medial/lateral: 4.5 mm to the bregma), according to a previous study ( Pan et al, 2017 ). The window was drilled to a target size of 4 mm × 3 mm using a dental drill, and saline (Taiwan Biotech Co., Ltd., Taoyuan, Taiwan) was applied each 5 min for cooling.…”