Local endovascular infusion and hypothermia in stroke therapy: A systematic review.

Ischemic stroke is a leading cause of death and disability worldwide, but there are no effective, widely applicable stroke therapies. Systemic hypothermia is an international mainstay of postcardiac arrest care, and the neuroprotective benefits of systemic hypothermia following cerebral ischemia have been proven in clinical trials, but logistical issues hinder clinical acceptance. As a novel solution to these logistical issues, the application of local endovascular infusion of cold saline directly to the infarct site using a microcatheter has been put forth. In small animal models, the procedure has shown incredible neuroprotective promise on the biochemical, structural, and functional levels, and preliminary trials in large animals and humans have been similarly encouraging. In addition, the procedure would be relatively cost-effective and widely applicable. The administration of local endovascular hypothermia in humans is relatively simple, as this is a normal part of endovascular intervention for neuroendovascular surgeons. Therefore, it is expected that this new therapy could easily be added to an angiography suite. However, the neuroprotective efficacy in humans has yet to be determined, which is an end goal of researchers in the field. Given the potentially massive benefits, ease of induction, and cost-effective nature, it is likely that local endovascular hypothermia will become an integral part of endovascular treatment following ischemic stroke. This review outlines relevant research, discusses neuroprotective mechanisms, and discusses possibilities for future directions.

Psychocardiological disorder and brain serotonin after comorbid myocardial infarction and depression: an experimental study.

Objectives We investigated whether trimetazidine pretreatment can regulate central and peripheral serotonin (5-HT) in rats of myocardial infarction (MI) combined with depression. Methods Forty rats were randomly assigned to a sham operation group (n = 10) and a disease model group (n = 30). The sham operation group was pretreated with normal saline for 4 weeks. The disease model group was randomly assigned further into a negative control subgroup, a positive control subgroup, and a treatment subgroup - the groups received saline, sertraline, and trimetazidine pretreatment, respectively, for 4 weeks, then the rats were subjected to MI combined with depression. 5-HT concentrations in the serum, platelet lysate, and cerebral cortex lysate were analyzed with ELISA. Results The levels of serum 5-HT and platelet 5-HT were significantly lower in negative control subgroup than the sham operation group (P < 0.05), but there was no significant difference in brain 5-HT (P > 0.05). Compared with the negative control subgroup, the levels of serum 5-HT and platelet 5-HT in the positive control subgroup and treatment subgroup were significantly higher (P < 0.05). The levels of 5-HT in brain of the positive control subgroup and treatment subgroup were significantly lower than those in the negative control subgroup (P < 0.05). Conclusions Trimetazidine pretreatment can increase serum and platelet 5-HT levels in rats with MI and depression and decrease 5-HT levels in brain tissue. This regulatory effect on central and peripheral 5-HT suggests a role for trimetazidine in the treatment of psychocardiological diseases.

Beneficial effects of trimetazidine on expression of serotonin and serotonin transporter in rats with myocardial infarction and depression.

BACKGROUND: Trimetazidine is an anti-ischemic drug that can inhibit platelet aggregation and regulate serotonin (5-hydroxytryptamine [5-HT]) release. The purpose of this study was to investigate the therapeutic effects of trimetazidine on 5-HT and serotonin transporter (SERT) expression in experimentally induced myocardial infarction (MI), depression, and MI + depression. MATERIALS AND METHODS: Eighty Sprague Dawley (SD) rats were randomly divided into a trimetazidine group and a saline group of 40 rats each. The trimetazidine group was given trimetazidine pretreatment for 4 weeks, while the saline group received saline for 4 weeks. Both groups were then subdivided into four subgroups (n=10), which were each subjected to a unique disease condition: sham surgery, MI, depression, or MI + depression. All rats were sacrificed 3 days thereafter, and serum and platelet levels of 5-HT and SERT were assessed. In addition, we experimented with trimetazidine posttreatment. Twenty SD rats underwent MI surgery, and were then randomly divided into a treatment and a saline group (n=10 each). For 4 weeks post-surgery, the trimetazidine group was given trimetazidine, while the saline group received saline. Serum and platelet levels of 5-HT and SERT were assessed. RESULTS: Pretreatment with trimetazidine: in the nontreatment saline group, MI, depression, and MI + depression showed significant declines (P<0.05) in both serum and platelet 5-HT levels compared to sham. Trimetazidine treatment significantly increased serum and platelet 5-HT levels in the MI, depression, and MI + depression (P<0.05) subgroups compared to their counterparts in the saline group. Results for SERT were heterogeneous between serum and platelets. Trimetazidine treatment significantly decreased serum levels of SERT in the sham surgery subgroup (P<0.05), while significantly increasing levels in depression rats, compared to control (P<0.05). In platelets, trimetazidine significantly decreased SERT in sham surgery, MI, depression, and MI + depression rats, compared to control (P<0.05). This contrast suggests that trimetazidine has opposite effects in serum and platelet SERT levels for the three disease models. Post-surgery trimetazidine: increased serum 5-HT (P<0.05) and serum SERT (P<0.05) were observed, compared to control. In platelets, trimetazidine decreased both 5-HT and SERT compared to control, significantly (P<0.05) for 5-HT, but not significantly for SERT (P>0.05). CONCLUSION: Trimetazidine has a regulatory effect on 5-HT and SERT in the serum and platelets. Because of the downstream effects of this regulation on blood vessel function and myocardial protection, trimetazidine may be a therapeutic or preventive agent in several disease processes, including MI, depression, and the comorbidity between these two diseases. Further investigation, aimed at exploring the clinical potential of trimetazidine, is therefore warranted.

Exercise rehabilitation immediately following ischemic stroke exacerbates inflammatory injury.

OBJECTIVES: The rehabilitative benefits of physical exercise after stroke appear to be contingent upon exercise initiation timing. The present study assessed the hypothesis that very early post-stroke exercise would amplify cellular stress and increases expression of pro-inflammatory mediators, while exercise initiated later would limit the inflammation associated with cerebral ischemia/reperfusion injury. METHODS: Adult rats were subjected to middle cerebral artery occlusion and subsequently assigned to one of seven groups: one sham injury control group, three stroke groups subjected to exercise initiated after 6, 24 hours, or 3 days of reperfusion, and three stroke groups not subjected to exercise. Expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were examined 3 and 24 hours after completion of exercise regimens (and at corresponding time points in non-exercise controls). Heat shock protein-70 (Hsp70) and hypoxia inducible factor-1α (HIF-1α) expression levels were also compared between exercise and non-exercise groups. RESULTS: Early post-stroke exercise was associated with increased expression of pro-inflammatory mediators (ICAM-1, VCAM-1, TNF-α, and IL-1ß) and increased expression of cell stress markers (Hsp70 and HIF-1α). Exercise initiated after 3 days of reperfusion was associated with decreased expression of these molecules. CONCLUSION: Post-stroke exercise, if too early, may result in elevated levels of cell stress and increased expression of pro-inflammatory cytokines, which may amplify the tissue damage associated with cerebral ischemia/reperfusion injury. The results shed light on the manner in which exercise initiation timing may affect post-stroke rehabilitation.