Hypothermia in Stroke Therapy: Systemic versus Local Application

Abstract

Presently, there are no efective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective beneits of hypothermia, and surfacecooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and eicacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identiies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well.

Targeting focal ischemic and hemorrhagic stroke neuroprotection: Current prospects for local hypothermia

“…These and other mechanistic differences between LH and systemic TH treatment paradigms need to be considered and addressed in the experimental design of studies moving forward, as the assumption that they are equivalent in terms of their physiological impacts on neuroprotective mechanisms will not aid in effective clinical translation. For a more comprehensive review of the mechanisms responsible for the effects of hypothermic treatment after stroke, readers are referred to excellent reviews by Wassink and colleagues (Wassink et al, 2018), Sun and colleagues (Sun et al, 2019), Schmitt and colleagues (Schmitt et al, 2014) Huber and colleagues (Huber et al, 2017), Kurisu and Yenari (Kurisu & Yenari, 2017), as well as Basto and Lyden (Basto & Lyden, 2018) and others (Lee et al, 2017; Sun et al, 2019; Wassink et al, 2018). We will now provide a summary of the current state of the LH field in treating focal stroke and evaluate several key future directions.…”

Regional cerebral infusion for acute ischemic stroke

“…In addition, there is a potential for harm if hypothermia is too deep or if infusion volumes are too large, so the depth, duration, and therapeutic window all require optimization if RCI is to gain clinical acceptance going forward. [11] Future investigations should focus on optimization of these variables as they likely play a significant role in the degree of benefit that RCI would provide to patients.…”

The cerebral circulation and cerebrovascular disease III: Stroke

“…[ 74 ] In addition, the inflammation caused by ischemia stimulates macrophages to release IL-1β and TNF-α, both of which increase production of MMPs that further facilitate BBB disruption. [ 68 75 ] Inflammation also impairs the autoregulatory properties of cerebral vessels, rendering them less able to compensate for hemostatic disturbances once the infarct area is reperfused. Ultimately, BBB disruption, when coupled with this diminished autoregulatory capacity, predisposes the vicinity of the infarct to blood extravasation into the brain parenchyma upon reperfusion.…”