Peripheral sensory stimulation is neuroprotective in a rat photothrombotic ischemic stroke model

Abstract

Ischemic stroke is one of the leading causes of death and disability in the world. Thrombolytic therapy using recombinant tissue plasminogen activator (rtPA), the only FDA-approved drug for acute ischemia, is limited by a narrow therapeutic time window and risk of hemorrhage. There is a serious need for a neuroprotective therapy which is clinically viable. We earlier demonstrated that peripheral sensory stimulation (PSS) is a potential therapeutic intervention for hyperacute ischemia resulting in recovery of neurovascular functions when administered immediately following ischemia onset in a rat model. Here, we investigated the potential neuroprotective effect of PSS during the hyperacute phase of stroke in a rat photothrombotic ischemia (PTI) model. We employed electrocorticography (ECoG) to image cortical neural activity responses pre-and post-ischemia. Results showed that the neural activity including somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were restored following administration of PSS. Further, immunohistochemistry and TTC staining also indicated the neuroprotective effect of PSS intervention, protecting more neurons and reduced infarct. Overall, the study demonstrated that PSS administered immediately following ischemia induction in a rat PTI model can significantly promote neuroprotection via inhibition of peri-infarct expansion and enhanced cortical neural activity functions, suggesting effective recovery. Future work utilizing multimodal imaging to probe changes in neurovascular functions, will explore application of PSS as an adjuvant intervention for improving rtPA thrombolysis therapy.

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.…”

Effectiveness of Sensory Stimulation on Sensory Function Among Patients with Stroke

“…In Tamil Nadu, the prevalence of cerebrovascular accident patient was 257/197,596 (100,000 = 130 per lakh), 1 out of 769 population affected by cerebrovascular accident. Males are more affected than females and hypertension was predominant cause of cerebrovascular accident (Bandla et al, 2016). The result from this study helps us to assess the rehabilitative need and to estimate the burden on cerebrovascular accident in rural area.…”

Sensory stimulation in acute stroke therapy

“…12,13 These findings have been independently repeated and also been demonstrated in aged Fisher 344 rats and with several anesthesia protocols. 13,14 Interestingly, the critical factors that determined the protective effect of sensory stimulation were not the length of stimulation—10 min of condensed stimulation were sufficient for total protection—but the timing and number of whiskers stimulated. 3,15 Sensory stimulation during the first 2–3 h after MCAO was protective which overlaps with the time window of thrombolysis therapy and thrombectomy.…”

“…2,12–14 Acute stimulation of the ischemic core has repeatedly been reported to protect the brain of rats entirely by an increased blood flow through anastomoses between the territories of cerebral arteries. 3,12–14 On the other hand, neuronal activation in the peri-infarct zone has been shown to lower oxygen levels thereby causing waves of depolarization and vasoconstriction in mice. 2 Via this mechanism, cerebral blood flow decreases and infarct volume increases by around 50%.…”