Ischemic Postconditioning Fails to Protect against Neonatal Cerebral Stroke

Abstract

The lack of efficient neuroprotective strategies for neonatal stroke could be ascribed to pathogenic ischemic processes differentiating adults and neonates. We explored this hypothesis using a rat model of neonatal ischemia induced by permanent occlusion of the left distal middle cerebral artery combined with 50 min of occlusion of both common carotid arteries (CCA). Postconditioning was performed by repetitive brief release and occlusion (30 s, 1 and/or 5 min) of CCA after 50 min of CCA occlusion. Alternative reperfusion was generated by controlled release of the bilateral CCA occlusion. Blood-flow velocities in the left internal carotid artery were measured using color-coded pulsed Doppler ultrasound imaging. Cortical perfusion was measured using laser Doppler. Cerebrovascular vasoreactivity was evaluated after inhalation with the hypercapnic gas or inhaled nitric oxide (NO). Whatever the type of serial mechanical interruptions of blood flow at reperfusion, postconditioning did not reduce infarct volume after 72 hours. A gradual perfusion was found during early re-flow both in the left internal carotid artery and in the cortical penumbra. The absence of acute hyperemia during early CCA re-flow, and the lack of NO-dependent vasoreactivity in P7 rat brain could in part explain the inefficiency of ischemic postconditioning after ischemia-reperfusion.

Sildenafil Mediates Blood-Flow Redistribution and Neuroprotection After Neonatal Hypoxia-Ischemia

“…25 More recently, Zhang et al 26 have shown that sildenafil can reduce the cognitive deficits associated with β-amyloid peptide-induced neuroinflammation in mice. In the present study, the transient improvement in the cerebral hemodynamic status by sildenafil, either by increasing plasma cGMP and NO metabolites 27 or by improving endothelial function after HI (impaired at P7), 28,29 leads to reduce injury and consequently to reduce inflammatory responses.…”

A Floating Bridge Disrupts Seaward Migration and Increases Mortality of Steelhead Smolts in Hood Canal, Washington State

“…Mortalities are likely caused by predation by a marine mammal, inferred from movement patterns recorded on HCB receivers that would be atypical of surviving steelhead smolts or tags consumed by avian predators. This study identifies an area of particular concern for steelhead smolts migrating out of Hood Canal, and perhaps explains part of the reason for low early marine survival rates [20], [21]. Increasing understanding of the interactions between habitat modification, prey migration, and predator responses to aggregation may support management of similar migratory bottlenecks, and informs future decisions about development and increasing human infrastructure in aquatic environments.…”

“…A detailed description of fish collection and tagging can be found in [20] and in [21]. Briefly, natural-origin steelhead smolts were collected at a weir across Big Beef Creek (2006–2010; N = 157), and at rotary screw traps in the South Fork Skokomish River (2006–2010; N = 98; hereafter “Skokomish River”), Hamma Hamma River (2007; N = 6) and the Dewatto River (2006, 2007; N = 54; Fig.…”

“…The pontoons span roughly 95% of the width of Hood Canal at low tide, forming a substantial barrier to aquatic organisms travelling near the water’s surface. Recent telemetry studies on migrating juvenile steelhead in Hood Canal [20], [21] have reported behavioral anomalies associated with the Hood Canal Bridge that indicate migration disruption. Vertical distributions of migrating steelhead smolts have not been well documented, but juvenile salmonids are known to primarily inhabit the upper 12 meters of the marine water column [24], and are thus likely to encounter the submerged pontoons of the Hood Canal Bridge (HCB).…”

“…Vertical distributions of migrating steelhead smolts have not been well documented, but juvenile salmonids are known to primarily inhabit the upper 12 meters of the marine water column [24], and are thus likely to encounter the submerged pontoons of the Hood Canal Bridge (HCB). In this paper we analyze data from five years of tagged steelhead outmigrations (2006–2010; [20], [21] to determine the probability that the Hood Canal Bridge impedes migration and contributes to extra mortality for steelhead smolts.…”