Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

Dengue virus (DENV) causes disease in millions of people annually and disproportionately affects those in the developing world. DENVs may be divided into four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and a geographical region may be affected by one or more DENV serotypes simultaneously. Infection with DENV may cause life-threatening disease such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), but more often causes less severe manifestations affecting a wide range of organs. Although many previous reports have explored the role of the different DENV serotypes in the development of severe manifestations, little attention has focused on the relative role of each DENV serotype in the development of cutaneous, respiratory, gastrointestinal, musculoskeletal, and neurological manifestations. We recruited a large group of participants from four countries in South America to compare the prevalence of more than 30 manifestations among the four different DENV serotypes. We found that certain DENV serotypes were often associated with a higher prevalence of a certain manifestation (e.g., DENV-3 and diarrhea) or manifestation group (e.g., DENV-4 and cutaneous manifestations)

Models of Traumatic Cerebellar Injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective

ATP signalling in epilepsy

This paper focuses on a role for ATP neurotransmission and gliotransmission in the pathophysiology of epileptic seizures. ATP along with gap junctions propagates the glial calcium wave, which is an extraneuronal signalling pathway in the central nervous system. Recently astrocyte intercellular calcium waves have been shown to underlie seizures, and conventional antiepileptic drugs have been shown to attenuate these calcium waves. Blocking ATP-mediated gliotransmission, therefore, represents a potential target for antiepileptic drugs. Furthermore, while knowledge of an antiepileptic role for adenosine is not new, a recent study showed that adenosine accumulates from the hydrolysis of accumulated ATP released by astrocytes and is believed to inhibit distant synapses by acting on adenosine receptors. Such a mechanism is consistent with a surround-inhibitory mechanism whose failure would predispose to seizures. Other potential roles for ATP signalling in the initiation and spread of epileptiform discharges may involve synaptic plasticity and coordination of synaptic networks. We conclude by making speculations about future developments

Does covid-19 impair endogenous neurogenesis?

Endogenous neural stem cells are thought to continue to generate new neurons throughout life in the human brain. Endogenous neurogenesis has been proposed to contribute to physiological roles in maintaining and regenerating olfaction, as well as promoting normal cognition, learning and memory. Specific impairments in these processes in COVID-19 - impaired olfaction and cognition - may implicate the SARS-CoV-2 virus in attenuating neurogenesis. Furthermore, neurogenesis has been linked with neuroregeneration; and impaired neuroregeneration has previously been linked with neurodegenerative diseases. Emerging evidence supports an association between COVID-19 infection and accelerated neurodegeneration. Also, structural changes indicating global reduction in brain size and specific reduction in the size of limbic structures - including orbitofrontal cortex, olfactory cortex and parahippocampal gyrus - as a result of SARS-CoV-2 infection have been demonstrated. This paper proposes the hypothesis that SARS-CoV-2 infection may impair endogenous neural stem cell activity. An attenuation of neurogenesis may contribute to reduction in brain size and/or neurodegenerative processes following SARS-CoV-2 infection. Furthermore, as neural stem cells are thought to be the cell of origin in glioma, better understanding of SARS-CoV-2 interaction with tumorigenic stem cells is indicated, with a view to informing therapeutic modulation. The subacute and chronic implications of attenuated endogenous neurogenesis are explored in the context of long COVID. Modulating endogenous neurogenesis may be a novel therapeutic strategy to address specific neurological manifestations of COVID-19 and potential applicability in tumour virotherapy. [Abstract copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.