Altered levels of PGF in cat spinal cord tissue following traumatic injury.

Previous studies by others indicated that PGs were present in brain, spinal cord, and c.s.f. of several mammalian species. In the present study we compared levels of PGE and PGF by R.I.A. in spinal cord tissue from traumatized cats and cats pretreated with indomethacin prior to trauma to those of baseline and sham operated controls in order to assess for the first time, to our knowledge, whether meaningful changes in levels of PGE and PGF could be detected which might shed new light on the etiology of spinal cord trauma. Levels of PGF (nanograms/gram wet wt) in the cord segment immediately adjacent to the point of trauma were 8.05 +/- 1.50, and 13.13 +/- 1.38 for baseline and sham operated cats respectively. Spinal trauma led to more than a 100% increase in PGF levels to 29.26 +/- 3.58. Although pretreatment with indomethacin 30 min prior to trauma gave the expected blockade of the PGF response to trauma, a measurable level of PGF (2.55 +/- 0.17) was found in the cord after indomethacin. Cord levels of PGF declined after 3 hr in both sham operated and traumatized animals. PGF was maximally stimulated by trauma during the first 3 hr with little effect at 72 hr. Although carefully examined, PGE levels in cat spinal cord appeared to be virtually unaffected by trauma. These findings clearly demonstrate for the first time that traumatic injury to the spinal cord is accompanied by marked increases in PG levels at the site of trauma, and that the observed elevation in PGF in response to trauma can be blocked by indomethacin in vivo. Whether PGF changes are causally related to the etiology of spinal cord trauma, or merely represent a manifestation of PG release as a result of non-specific tissue injury, remains to be seen.     

High dose Erythropoietin increases brain tissue oxygen tension in Severe Vasospasm after Subarachnoid Hemorrhage

ABSTRACT: BACKGROUND: Vasospasm-related delayed cerebral ischemia (DCI) significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH). Erythropoietin (EPO) may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2). METHODS: Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM) received systemic EPO therapy (30.000 IU per day for 3 consecutive days) for severe cerebral vasospasm. Cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), intracranial pressure (ICP), PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. RESULTS: A total of 22 interventions were analyzed. Median age was 47 years (32-68) and 86% were female. Three patients (38%) developed DCI. MAP slightly decreased 2 hours after intervention (P<0.04) without significantly affecting CPP and ICP. PbtO2 significantly increased over time (P<0.05) to a maximum of 7+/-4mmHg increase 16 hours after infusion. Brain metabolic parameters did not change over time. CONCLUSIONS: EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.     

心脏术后急性肾损伤的研究进展

急性肾损伤（Acute Kidney Injury,AKI）是心脏术后较常见且较严重的并发症,明显增加患者的住院费用,并且增加手术死亡率。研究发现术前肾功能不全、糖尿病、及外周血管疾病等是术后AKI的危险因素。最新的研究发现一些新的生物学标准物可以为我们早期诊断心脏术后AKI的发生的提供帮助。而一旦出现AKI,选择适当药物治疗和肾脏替代治疗,可以保护肾功能,改善AKI患者的预后。     

Pathogenic natural antibodies propagate cerebral injury following ischemic stroke in mice

Self-reactive natural Abs initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the postischemic brain and the role of natural Abs in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in Ab-deficient Rag1(-/-) mice after 60 min of middle cerebral artery occlusion and reperfusion. Reconstitution with C2 or B4 mAb in otherwise protected Rag1(-/-) mice restored injury to that seen in wild-type (wt) mice, as demonstrated by infarct volume, demyelination, and neurologic scoring. IgM deposition was demonstrated in both wt mice and reconstituted Rag1(-/-) mice, and IgM colocalized with the complement activation fragment C3d following B4 mAb reconstitution. Further, recombinant annexin IV significantly reduced infarct volumes in wt mice and in Rag1(-/-) mice administered normal mouse serum, demonstrating that a single Ab reactivity is sufficient to develop cerebral ischemia reperfusion injury in the context of an entire natural Ab repertoire. Finally, C2 and B4 mAbs bound to hypoxic, but not normoxic, human endothelial cells in vitro. Thus, the binding of pathogenic natural IgM to postischemic neoepitopes initiates complement-dependent injury following murine cerebral ischemia and reperfusion, and, based also on previous data investigating IgM reactivity in human serum, there appears to be a similar recognition system in both mouse and man.