Corpus callosum in COVID-19 cytokinopathy, an update

The corpus callosum (CC) connects frontal, parietal, occipital and temporal cortices in the brain. We report a disconnection syndrome as a manifestation of coronavirus disease 2019 (COVID-19) encephalopathy. Like prior coronaviridae, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the brain over a spectrum of injury. Present communication is the first description of white matter involvement confined to CC’s commissural fibers in their entirety. Until case registries, longitudinal studies and animal models clarify any direct neurotropism of SARS-CoV-2; this case is consistent with recent biological evidence suggesting a cytokine mediated excitotoxic injury concomitant with the severity of infection.

Superoxide dismutase reduces monosodium glutamate-induced injury in an organotypic whole hemisphere brain slice model of excitotoxicity

Background Knowledge of glutamate excitotoxicity has increased substantially over the past few decades, with multiple proposed pathways involved in inflicting damage. We sought to develop a monosodium glutamate (MSG) exposed ex vivo organotypic whole hemisphere (OWH) brain slice model of excitotoxicity to study excitotoxic processes and screen the efficacy of superoxide dismutase (SOD). Results The OWH model is a reproducible platform with high cell viability and retained cellular morphology. OWH slices exposed to MSG induced significant cytotoxicity and downregulation of neuronal excitation-related gene expression. The OWH brain slice model has enabled us to isolate and study components of excitotoxicity, distinguishing the effects of glutamate excitation, hyperosmolar stress, and inflammation. We find that extracellularly administered SOD is significantly protective in inhibiting cell death and restoring healthy mitochondrial morphology. SOD efficacy suggests that superoxide scavenging is a promising therapeutic strategy in excitotoxic injury. Conclusions Using OWH brain slice models, we can obtain a better understanding of the pathological mechanisms of excitotoxic injury, and more rapidly screen potential therapeutics.

Inhibition of the Adenosine A2A Receptor Mitigates Excitotoxic Injury in Organotypic Tissue Cultures of the Rat Cochlea

The primary loss of cochlear glutamatergic afferent nerve synapses due to noise or ageing (cochlear neuropathy) often presents as difficulties in speech discrimination in noisy conditions (hidden hearing loss (HHL)). Currently, there is no treatment for this condition. Our previous studies in mice with genetic deletion of the adenosine A2A receptor (A2AR) have demonstrated better preservation of cochlear afferent synapses and spiral ganglion neurons after noise exposure compared to wildtype mice. This has informed our current targeted approach to cochlear neuroprotection based on pharmacological inhibition of the A2AR. Here, we have used organotypic tissue culture of the Wistar rat cochlea at postnatal day 6 (P6) to model excitotoxic injury induced by N-methyl-d-aspartate (NMDA)/kainic acid (NK) treatment for 2 h. The excitotoxic injury was characterised by a reduction in the density of neural processes immediately after NK treatment and loss of afferent synapses in the presence of intact sensory hair cells. The administration of istradefylline (a clinically approved A2AR antagonist) reduced deafferentation of inner hair cells and improved the survival of afferent synapses after excitotoxic injury. This study thus provides evidence that A2AR inhibition promotes cochlear recovery from excitotoxic injury, and may have implications for the treatment of cochlear neuropathy and prevention of HHL.