Objective: It is well known that residual cortical cerebral blood flow plays a pivotal role in the pathophysiology of cerebral ischemia and can influence the outcome of recanalization therapy. This study examined the impact of residual cortical cerebral blood flow on the neuroprotective efficacy of human albumin in a rat transient cerebral ischemia model. Methods: Sprague–Dawley rats were subjected to 2 hour middle cerebral artery occlusion. According to different magnitudes of residual cortical cerebral blood flow during cerebral ischemia, rats were divided into three groups: Group I, cerebral blood flow <25% of the baseline; Group II, cerebral blood flow between 25 and 50% of the baseline; Group III, cerebral blood flow >50% of the baseline. The infarct volume and brain swelling were observed after 48 hours of reperfusion. Neurological scores and motor function were also evaluated. Results: After 2 days of reperfusion, human albumin therapy significantly (p<0.01) reduced total infarct volume and improved the neurological and motor function compared with the stroke group only in Group II. In Group I and in Group III, whether human albumin was administered or not, rats in Group I always showed a poor outcome and rats in Group III always showed an excellent outcome. Conclusion: Our study suggests that human albumin has neuroprotection in acute stroke treatment only within a magnitude range of residual cortical cerebral blood flow during ischemia.
Abstract Background and purposes : Optimal treatment approaches for patients with both patent foramen ovale (PFO) and hypercoagulable state remain uncertain. This study aimed to introduce a novel therapeutic strategy involving the combination of anticoagulant and antiplatelet medications following PFO closure. Methods Consecutive patients diagnosed as PFO and hypercoagulable state were enrolled in this real-world case-control study between January 2021 and January 2022. After PFO closure, patients received either a combination of anticoagulant and mono antiplatelet therapy (anticoagulant group)or dual antiplatelet therapy(antiplatelet group) as part of their post-procedural management. Follow-up outcomes encompassed cessation of clinical symptoms, recurrence of neurological events, major bleeding episodes, and mortality. Results The final analysis comprised 38 eligible patients. Following PFO closure, of whom 17 patients were treated with a combination of anticoagulant and mono antiplatelet therapy, others treated with dual antiplatelet therapy. Over the one-year treatment period, significant differences were observed in alleviating migraine and prevention of recurrent stroke between the anticoagulant group and the antiplatelet group (p < 0.05). No instances of bleeding events and recurrent stroke were recorded during follow-up. Conclusions For patients with both PFO and hypercoagulable state, long-term therapy involving anticoagulants and mono antiplatelet agents post PFO closure may be a viable option. However, further validation through multicenter and extensive clinical trials is warranted.
Despite the fact that over 200 phosphorylation sites have been mapped on the mitochondrial oxidative phosphorylation (OxPhos) complexes, very little is known about the relevant cell signaling pathways and the terminal kinases and phosphatases that control these phosphorylations. Within OxPhos, cytochrome c (Cytc) plays a special role because it is not only involved in electron transport but is also a key executer of apoptosis when it is released from the mitochondria. It is therefore not surprising that Cytc is regulated by phosphorylation. Four phosphorylation sites have been mapped on mammalian Cytc, two of which have been studied functionally, demonstrating that both respiration and apoptosis are under the control of signaling pathways that have yet to be identified. We here review the regulation and multiple functions of mammalian Cytc, including respiration, reactive oxygen species (ROS) scavenging under healthy conditions, ROS production via p66, and cardiolipin oxidation during apoptosis. We propose targeting Cytc by manipulation of signaling cascades as a therapeutic avenue in conditions including neurodegeneration and cancer. Abbreviations: Apaf-1, apoptotic protease-activating factor 1; CPP, cell-penetrating peptide; COX, cytochrome c oxidase; Cytc, cytochrome c; Cytc-T, testes cytochrome c; ΔΨm, mitochondrial membrane potential; ETC, electron transport chain; OxPhos, oxidative phosphorylation; ROS, reactive oxygen species.
Background: Therapeutic hypothermia as a neuroprotective strategy after stroke has been well established in animal models, but its application in humans has been limited by logistical challenges. To provide a solution to these challenges, this study was designed to determine the hypothermic and neuroprotective efficacy of infusing cold saline directly into the internal jugular (IJ) vein, and compare the effects of IJ regional cerebral hypothermia to those achieved by intra-carotid (IC) artery regional hypothermia in an ischemic stroke model. Methods: Middle cerebral artery occlusion was established in rats using an intraluminal filament. Regional cerebral hypothermia was then achieved by infusion of 6 ml of 0 °C isotonic saline by micro-catheter into the right IJ or right IC for 30 minutes immediately after the initiation of reperfusion. Infarct sizes, neurological deficits, edema volume, blood brain barrier (BBB) damage, BBB associated molecules (MMP-9 and AQP-4), and apoptosis associated proteins (Bcl-2 and cleaved Caspase-3) were measured. Results: Both IJ and IC infusion led to a significant, rapid reduction in brain temperatures while having a minimal effect on rectal temperatures. Infarct sizes were significantly reduced at 24 hours after reperfusion by IC and IJ treatments. Neurologic deficits were also significantly improved by IC and IJ infusion compared to control models over a 28-day observation period. Both IC and IJ significantly reduced Evans Blue leakage and edema volume compared with control groups. MMP-9 and AQP-4 expression were also reduced, Bcl-2 increased, and cleaved Caspase-3 decreased in the IC and IJ groups. Conclusion: Compared to IC infusion, IJ infusion conferred a similar degree of regional cerebral hypothermia and neuroprotection following ischemic stroke. Given the ease of establishing vascular access via the internal jugular vein and the powerful neuroprotection that hypothermia provides, IJ regional brain cooling could be utilized as a promising hypothermia-induction modality due to its safe, quick, and effective features.
Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We developed a new rat model to study intracranial atherosclerosis.Twelve-week-old male Sprague-Dawley rats were divided into a control (on a maintain diet) and a high-cholesterol group (on a daily 1% cholesterol diet) for up to 6 weeks. During the first two weeks, NG-nitro-L-arginine methylester (L-NAME, 3 mg/mL) was added to the drinking water in the high-cholesterol group to induce intimal changes making the rats susceptible to atherosclerosis. Blood lipids, including low-density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG), and high-density lipoprotein (HDL), were measured after 3 and 6 weeks. Histological sections of the brains, including internal carotid artery (ICA), middle cerebral artery (MCA), and basilar artery (BA), were prepared to study intracranial artery morphometry and intimal thickening. The levels of CD68, an inflammatory marker, within the vessel walls as determined by immunohistochemistry were also measured.The high-cholesterol diet increased the levels of classic blood markers of atherosclerosis, LDL, CHO, and TG as well as decreased HDL, which became progressively more intensive with time. Rats showed increased intimal thickening in the ICA, MCA, and BA. This protocol also increased the levels of CD68 immunoreactivity within the vessel walls.A rat model of intracranial atherosclerosis was effectively developed by high-cholesterol diet and L-NAME administration. This clinically relevant model would be beneficial for studying ICAS.
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