Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke

Abstract

Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential.

Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

“…Based on work in animal models, penetrating arterioles that supply the cortical surface represent a key bottleneck in cerebral blood flow and a site of vulnerability (Black et al, 2009;Shih et al, 2013). Rodents appear to have particular redundancies in their vasculature, where anastomoses can be recruited to salvage ischemic tissue through activity-dependent neuroprotection (Lay et al, 2010). It is unclear whether humans benefit from such extensive vascular redundancy; however, the possibility of engaging collateral circulation by restricting flow to the periphery has been explored as a potential stroke intervention (Shuaib et al, 2011;Winship et al, 2014).…”

Neurovascular Coupling Varies with Level of Global Cerebral Ischemia in a Rat Model

“…This observation suggests that, at least in global ischemia, oxygen delivery and consumption increases caused by stimulation become more balanced with ischemic severity. If the same is true in focal ischemia, then the mechanism for the neuroprotection of functional stimulation during ischemia reported in the literature 8,9 is probably not related to CBF changes. However, the potential for activation of collateral blood flow through leptomeningeal anastomoses during functional stimulation in focal ischemia necessitates that similar data be collected in focal ischemia models.…”

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

“…In order to stabilize the thrombus, the stimulation treatment in the various groups was onset only after an interval, following successful induction of PTI stroke. 36,37 The P1 (the first positive peak after forepaw stimulation) amplitude, N1 (the first negative peak directly following P1) amplitude, and peak-to-peak amplitude were extracted from the averaged SSEPs [ Fig. 1(c)].…”

“…The control group involved only PTI stroke induction but no forepaw stimulation treatment. 36,37 Hence, plots of SSEP components are included only for the four experimental groups and not for the control group. All the evaluations were based on Ch4 because it is located in the iS1FL hemisphere, in close proximity to the targeted PTI stroke location.…”