Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous EPO with soluble EPO-R exacerbated ischemic injury, which supports a crucial role for an endogenous EPO͞EPO-R system in the survival and recovery of neurons after an ischemic insult. Systemic administration of rhEPO before or immediately after retinal ischemia not only reduced histopathological damage but also promoted functional recovery as assessed by electroretinography. Exogenous EPO also significantly diminished terminal deoxynucleotidyltransferase-mediated dUTP end labeling labeling of neurons in the ischemic retina, implying an antiapoptotic mechanism of action. These results further establish EPO as a neuroprotective agent in acute neuronal ischemic injury. E rythropoietin (EPO) has been viewed traditionally as a hematopoietic cytokine produced by the fetal liver and adult kidney in response to hypoxia. Results of recent studies now support a physiological role for EPO within the central nervous system. The expression of EPO and EPO receptors (EPO-Rs) in the central nervous system and the up-regulation of EPO by hypoxia͞ischemia in vitro and in vivo suggest that this cytokine is an important mediator of the brain's response to injury. Consistent with this hypothesis, pretreatment with exogenous EPO protects cultured neurons from hypoxia (1, 2), glutamate excitotoxicity (3), and growth-factor withdrawal (2). When administered systemically, EPO can cross the blood-brain barrier and reduce neuronal injury in animal models of focal ischemic stroke, traumatic brain injury, inflammation, kainate toxicity, and spinal cord injury (2, 4, 5). EPO rescues neurons from acute injury at least in part by inhibiting apoptosis via activation of specific protein kinase pathways (2) and the recruitment of NF-B (6).Prior studies of EPO in different models of brain injury raise the possibility that this cytokine may participate in the recovery of retinal neurons from ischemia. Retinal ischemia is a serious and common clinical problem. It occurs as a result of acute vascular occlusion and leads to visual loss in a number of ocular diseases such as acute glaucoma (7), diabetic retinopathy (8), and hypertensive vascular disease (9). Transient global retinal ischemia, for example, shares many similarities with transient global cerebral ischemia. Both cause selective damage of specific subpopulations of neurons. Pyramidal neurons in the CA-1 zone of the hippocampus are selectively vulnerable to trans...

Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and endothelial isoforms are constitutively expressed, and require calcium for activation. Both of these isoforms can be induced (i.e., new protein synthesis occurs) under appropriate conditions. The immunologic isoform is not constitutively expressed, and requires induction usually by immunologic activation; calcium is not necessary for its activation. Neuronal and immunologic NOS have been detected in the retina. Neuronal NOS may be responsible for producing nitric oxide in photoreceptors and bipolar cells. Nitric oxide stimulates guanylate cyclase of photoreceptor rod cells and increases calcium channel currents. In the retina of cats, NOS inhibition impairs phototransduction as assessed by the electroretinogram. Inducible nitric oxide synthase, found in Müller cells and in retinal pigment epithelium, may be involved in normal phagocytosis of the retinal outer segment, in infectious and ischemic processes, and in the pathogenesis of diabetic retinopathy. Nitric oxide contributes to basal tone in the retinal circulation. To date, findings are conflicting with respect to its role in retinal autoregulation. During glucose and oxygen deprivation, nitric oxide may increase blood flow and prevent platelet aggregation, but it may also mediate the toxic effects of excitatory amino acid release. This reactive, short-lived gas is involved in diverse processes within the retina, and its significance continues to be actively studied.

The results confirm the clinical suspicion that the risk of POVL is higher in cardiac and spine fusion surgery and show for the first time a higher risk of this complication in patients undergoing lower extremity joint replacement surgery. The prevalence of POVL in the eight most commonly performed surgical operations in the United States has decreased between 1996 and 2005. Increased odds of POVL with male gender and comorbidity index indicate that some risk factors for POVL may not presently be modifiable. The conclusions of this study are limited by factors affecting data accuracy, such as lack of data on the intraoperative course and inability to confirm the diagnostic coding of any of the discharges in the database.