COVID-19 as a Trigger of Recurrent Guillain-Barré Syndrome.

Coronavirus 2019 (COVID-19) has been reported to trigger Guillain-Barré syndrome (GBS). While uncommon, recurrent GBS (rGBS) episodes, triggered by antecedent viral infections, have been reported in a small proportion of GBS patients, here we describe a patient with a recurrent case of GBS, occurring secondary to COVID-19 infection. Before this patient's episode, he had two prior GBS flares, each precipitated by a viral infection followed by complete recovery besides intermittent paresthesias. We also consider the nosology of this illness in the spectrum of rGBS and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with their differing natural histories, prognosis, and therapeutic approaches. For patients who have a history of inflammatory demyelinating polyradiculopathies who develop COVID-19, we recommend close observation for neurologic symptoms over the next days and weeks.

Thermoregulation in brain injury.

Different mechanisms explain thermoregulatory dysfunction following ischemic stroke, hemorrhagic stroke, and traumatic brain injury. Temperature instability following brain injury likely involves hypothalamic injury, pathologic changes in cerebral blood flow, metabolic derangement, and a neurogenic inflammatory response. Although targeted temperature management (TTM) exerts pleiotropic effects, the heterogeneity of brain injury has hindered identification of patient subsets most likely to benefit from TTM. Early optimism about TTM's role in brain injury has been tempered by the failure of successive clinical trials to show improved patient outcomes. However, given the deleterious effects of fever, aggressive fever management is still warranted in the critically ill neurologic patient.

Blockade of receptor for advanced glycation end product attenuates pulmonary reperfusion injury in mice.

OBJECTIVE: The receptor for advanced glycation end products (RAGE) is expressed at high levels in the lung, particularly in type 1 alveolar cells, and has been shown to amplify injury triggered by acute stress. Previous studies suggest serum concentrations of soluble RAGE increase during pulmonary reperfusion injury after transplantation. RAGE blockade has been shown to suppress hepatic and cardiac ischemia and reperfusion injury in mice. Thus we tested the hypothesis that RAGE mediates tissue-injury mechanisms in ischemia and reperfusion injury in the lung. METHODS: C57BL/6 mice were subjected to 30 minutes of pulmonary ischemia by clamping the left hilum, followed by 60 minutes of reperfusion. Lung function was assessed by means of blood gas analysis, and capillary leak was assessed by injecting fluorescein isothiocyanate-labeled albumin and comparing fluorescence in bronchial lavage fluid with that in serum. Histologic analysis of the lung was performed by a pathologist naive to the experimental conditions. RESULTS: In animals subjected to RAGE blockade, significant increases in Po(2) (108 vs 73 mm Hg, P = .0094) and more than 3-fold decrease in capillary leak Relative Fluorescent Units (RFU, 6.12 vs 1.75; P = .001) were observed. Histologic examination revealed significant injury reduction in soluble RAGE-treated animals versus control animals. RAGE knockout mice exhibited a protected phenotype when exposed to pulmonary ischemia and reperfusion. Additionally, interleukin 8 production and nuclear factor kappaB activation were increased in control mice. CONCLUSION: Abrogation of RAGE signaling attenuates pulmonary ischemia and reperfusion injury. This study suggests that RAGE might play a central role in pulmonary reperfusion injury and in transplantation and that blockade of RAGE might offer a potential target to abrogate pulmonary reperfusion injury in clinical transplantation.

ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice.

Glioblastoma multiforme is the most common and lethal form of primary brain cancer. Diagnosis of this advanced glioma has a poor prognosis due to the ineffectiveness of current therapies. Aberrant expression of receptor tyrosine kinases (RTK) in glioblastoma multiformes is suggestive of their role in initiation and maintenance of these tumors of the central nervous system. In fact, ectopic expression of the orphan RTK ROS is a frequent event in human brain cancers, yet the pathologic significance of this expression remains undetermined. Here, we show that a glioblastoma-associated, ligand-independent rearrangement product of ROS (FIG-ROS) cooperates with loss of the tumor suppressor gene locus Ink4a;Arf to produce glioblastomas in the mouse. We show that this FIG-ROS-mediated tumor formation in vivo parallels the activation of the tyrosine phosphatase SH2 domain-containing phosphatase-2 (SHP-2) and a phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling axis in tumors and tumor-derived cell lines. We have established a fully penetrant preclinical model for adult onset of glioblastoma multiforme in keeping with major genetic events observed in the human disease. These findings provide novel and important insights into the role of ROS and SHP-2 function in solid tumor biology and set the stage for preclinical testing of targeted therapeutic approaches.

Touchscreen-enhanced visual learning in rats.

The efficiency of traditional levers and of modern touchscreen technology for training rats on a computerized visual discrimination was studied in a series of observations. When compared with a lever-based discrimination procedure, the use of touchscreens supported the faster development of signal tracking behavior and acquisition of a two-stimulus simultaneous visual discrimination. It did not affect the final level of accuracy. Factors related to spatial proximity of the responses with the stimuli, sign-tracking, and increased ease of touchscreen motor responses were suggested as possible reasons for the touchscreen training advantage. This increased efficiency allows large numbers of animals to be tested quickly, a necessary requirement for studies involving genetic and physiological interventions.