Search

Acid-sensing ion channel 1a (ASIC1a) is a proton-activated channel that is expressed ubiquitously throughout the central nervous system and in various types of immune cells. Its role in spinal cord injury (SCI) is controversial; inhibition of ASIC1a has been reported to improve SCI pathology in vivo, but conversely, gene ablation increased kainite-mediated excitotoxic cell death in vitro. Here, we re-examined the role of ASIC1a in a mouse model of SCI. First, we observed functional outcomes up to 42 days post-operation (DPO) in SCI mice with a selective genetic ablation of ASIC1a. Mice lacking ASIC1a had significantly worsened locomotor ability and increased lesion size compared with mice possessing the ASIC1a gene. Next, we explored pharmacological antagonism of this ion channel by administering the potent ASIC1a inhibitor, Hi1a. Consistent with a role for ASIC1a to attenuate excitotoxicity, accelerated neuronal cell loss was found at the lesion site in SCI mice treated with Hi1a, but there were no differences in locomotor recovery. Moreover, ASIC1a inhibition did not cause significant alterations to neutrophil migration, microglial density, or blood–spinal cord barrier integrity. [ABSTRACT FROM AUTHOR]

Following a spinal cord injury (SCI), secondary damage mechanisms are triggered that cause inflammation and cell death. A key component of this secondary damage is a reduction in local blood flow that initiates a well-characterised ischemic cascade. Downstream hypoxia and acidosis activate acid sensing ion channel 1a (ASIC1a) to trigger cell death. We recently showed that administration of a potent venom-derived inhibitor of ASIC1a, Hi1a, leads to tissue sparing and improved functional recovery when delivered up to 8 h after ischemic stroke. Here, we use whole-cell patch-clamp electrophysiology in a spinal cord slice preparation to assess the effect of acute ASIC1a inhibition, via a single dose of Hi1a, on intrinsic membrane properties and excitatory synaptic transmission long-term after a spinal cord hemisection injury. We focus on a population of interneurons (INs) in the deep dorsal horn (DDH) that play a key role in relaying sensory information to downstream motoneurons. DDH INs in mice treated with Hi1a 1 h after a spinal cord hemisection showed no change in active or passive intrinsic membrane properties measured 4 weeks after SCI. DDH INs, however, exhibit significant changes in the kinetics of spontaneous excitatory postsynaptic currents after a single dose of Hi1a, when compared to naive animals (unlike SCI mice). Our data suggest that acute ASIC1a inhibition exerts selective effects on excitatory synaptic transmission in DDH INs after SCI via specific ligand-gated receptor channels, and has no effect on other voltage-activated channels long-term after SCI. [ABSTRACT FROM AUTHOR]

We are all familiar with the expression, the 'importance of a good night's sleep', and work in the field of circadian biology and sleep over the last 30 years has shown this to be true. Under normal conditions, our sleep and circadian rhythms are synchronised and prepare the body for the varied demands of the 24-hour rotation of the earth on its axis. This synchronisation (entrainment) of our sleep and circadian rhythms to the daily light/dark cycle depends upon our eyes. Eye healthcare providers are often consulted about screen use and its impact on ocular health, as well as the potential effects on sleep and circadian rhythms of viewing electronic devices at night. It is important to remember that the eye is not only an organ of vision, but also provides us with our sense of time, utilising specialised cells within the retina called photosensitive retinal ganglion cells (pRGCs). Exposing the pRGCs to light at the wrong time of the day may cause disruption of normal circadian rhythms and sleep. In this review, we give a brief overview of sleep as part of an individual's circadian biology with special emphasis on the role of the eye. We discuss the impact of blue light and medications on sleep and review the evidence for toxicity of short-wavelength light on the retina. We emphasise the importance of sleep for good ocular health, briefly discuss the impact of ocular disease on sleep and note the optimal timing of corticosteroids and prostaglandins. [ABSTRACT FROM AUTHOR]