Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Changes in terminal sprout formation in rat sternocostalis muscle during chronic intoxication with 2,5 hexanedione

Qualitative and quantitative morphological studies of the sternocostalis muscle innervation were made on rats chronically intoxicated with 2,5 hexanedione (2,5 HD) using the zinc iodide\u2010osmium (ZIO) technique. Two distinct phases were seen in the events at the motor endplate. First, the number of motor endplates forming spontaneous terminal sprouts was found to increase linearly with time and, from the third week onward, the sprouts appeared to become progressively elongated. This latter change was associated with the appearance of swollen axons wihtin intramuscular nerve bundles. Second, from the sixth week onward, wallerian degeneration of nerve fibers was seen and terminal sprouts began to make new arborizations on muscle fibers. By the eighth week, this occurred in as many as 66% of the rats, and collateral sprouting was also observed at this time. The occurrence of increased spontaneous terminal sprouting due to altered neuromuscular function is discussed in the light of axonal changes resulting from nerofilament accumulation following 2,5 HD intoxication. Copyright \ua9 1984 John Wiley & Sons, Inc

Selective degeneration of cerebellar cortical neurons caused by cycad neurotoxin, L-β-methylaminoalanine (L-BMAA), in rats

Both the racemate and the L-form of BMAA (beta-methylaminoalanine), when injected intraperitoneally into young rats, produced acute signs of cerebellar dysfunction and degeneration of cerebellar stellate, basket, Purkinje and Golgi cells, but not granule cells. Degenerative changes were also occasionally seen in cerebellar roof nuclei which may be secondary in nature. No other changes were found in the remainder of the central nervous system. The doses of the L-form of BMAA producing these changes were from 6 to 14 mumols/g body weight, i.e. the lower and upper levels of the dose range used by Vega and Bell (1967) and equivalent to 75 and 183 mg/rat. Doses of 1 to 4 mg/g body weight of the racemate were given to young rats less than 100 g in weight, but no changes were apparent after daily doses of the racemate of 0.5 mg/g body weight. Damage to cerebellar neurons is considered to be the result of excitotoxic activity. All cells showing degeneration are GABAergic, although not all are known to possess N-methyl-D-aspartate (NMDA) receptors. The present finding of selective cerebellar neuron damage may not conflict with the earlier findings of others, but our results suggest that L-BMAA has unusual glutamate receptor binding properties