No abstract

Introduction: The 70-kDa heat shock protein (Hsp70) is a cytosolic chaperone which facilitates protein folding, degradation, complex assembly, and translocation. Following stroke, these functions have the potential to lead to cytoprotection, and this has been demonstrated using genetic mutant models, direct gene transfer or the induction of Hsp70 via heat stress, approaches which limit its translational utility. Recently, the investigation of Hsp70-inducing pharmacological compounds, which, through their ability to inhibit Hsp90, has obvious clinical implications in terms of potential therapies to mitigate cell death and inflammation, and lead to neuroprotection from brain injury. Areas covered: In this review, we will focus on the role of Hsp70 in cell death and inflammation, and the current literature surrounding the pharmacological induction in acute ischemic stroke models with comments on potential applications at the clinical level. Expert opinion: Such neuroprotectants could be used to synergistically improve neurological outcome or to extend the time window of existing interventions, thus increasing the numbers of stroke victims eligible for treatment.

Dexmedetomidine has emerged as a promising organ protective agent. We performed prospective randomized placebo-controlled trial investigating effects of perioperative dexmedetomidine infusion on pulmonary function following thoracic aortic surgery with cardiopulmonary bypass and moderate hypothermic circulatory arrest. Fifty-two patients were randomized to two groups: the dexmedetomidine group received 1 µg/kg of dexmedetomidine over 20 min after induction of anesthesia, followed by 0.5 µg/kg/h infusion until 12 h after aortic cross clamp (ACC)-off, while the control group received the same volume of normal saline. The primary endpoints were oxygenation indices including arterial O2 partial pressure (PaO2) to alveolar O2 partial pressure ratio (a/A ratio), (A–a) O2 gradient, PaO2/FiO2 and lung mechanics including peak inspiratory and plateau pressures and compliances, which were assessed after anesthesia induction, 1 h, 6 h, 12 h, and 24 h after ACC-off. The secondary endpoints were serum biomarkers including interleukin-6, tumor necrosis factor-α, superoxide dismutase, and malondialdehyde (MDA). As a result, dexmedetomidine did not confer protective effects on the lungs, but inhibited elevation of serum MDA level, indicative of anti-oxidative stress property, and improved urine output and lower requirements of vasopressors.

Background: Acute lung injury (ALI) is the most serious complication of subarachnoid hemorrhage (SAH). We investigated role of autophagy and inflammatory signaling pathways in lung damage and therapeutic effects of dexmedetomidine (DEX).Methods: Fifty male Wistar rats were randomly divided into five groups: sham, SAH, SAH+ DEX5, SAH+DEX25, and SAH+DEX50. SAH was induced using endovascular perforation technique. All rats received mechanical ventilation for 60 minutes. At 2 and 24 h of SAH induction, SAH+DEX groups were treated with 5, 25, and 50 µg/kg of dexmedetomidine, respectively.Histological ALI score and pulmonary edema were assessed after 48 hours. Lung expression of LC3B, ATG3, p62, TLR4, TLR9, and NFκB was assessed using western blotting and quantitative PCR. Blood levels of IL-6, IL-1β, IFN-γ, and TNFα were also assessed.Results: SAH induced ALI and pulmonary edema, which were attenuated in SAH+DEX5 (P<0.001 for both) and SAH+DEX25 groups (P=0.001 and P<0.001 for ALI and edema, respectively). Lung expressions of LC3B and ATG3 were upregulated in SAH group, which was attenuated in SAH+DEX5 and SAH+DEX25 groups. Lung expressions of TLR4, TLR9, and NFκB were increased in SAH group, which was attenuated in SAH+DEX5 group. Blood IL-6 level was increased in SAH group and attenuated in SAH+DEX5 and SAH+DEX25 groups. Blood IFN-γ level was lower in SAH group than in sham group, and it was increased in SAH+DEX25 group.Conclusions: Low-dose DEX treatment after SAH may protect against ALI by disrupting pathological brain-lung crosstalk and alleviating autophagy flux and TLR-dependent inflammatory pathways.