#brain: The mysterious origins of microglia

The origin of microglia, the resident macrophage population of the CNS, has been a long-standing matter of debate. Here we discuss two seminal studies published in 2007 in Nature Neuroscience that significantly contributed to a better understanding of microglia ontogeny and homeostasis in the adult brain.
Ginhoux F, Garel S. The mysterious origins of microglia. Nat. Neurosci. 2018 Jul;21(7):897-899. doi: 10.1038/s41593-018-0176-3.

Viral Triggers and Inflammatory Mechanisms in Pediatric Epilepsy. Review

Experimental and clinical findings suggest a crucial role for inflammation in the onset of pediatric seizures; this mechanism is not targeted by conventional antiepileptic drugs and may contribute to refractory epilepsy. Several triggers, including infection with neurotropic viruses such as human herpesvirus 6 (HHV-6), other herpesviruses, and picornaviruses, appear to induce activation of the innate and adaptive immune systems, which results in several neuroinflammatory responses, leading to enhanced neuronal excitability, and ultimately contributing to epileptogenesis. This review discusses the proposed mechanisms by which infection with herpesviruses, and particularly with HHV-6, and ensuing inflammation may lead to seizure generation, and later development of epilepsy. We also examine the evidence that links herpesvirus and picornavirus infections with acute seizures and chronic forms of epilepsy. Understanding the mechanisms by which specific viruses may trigger a cascade of alt…

Differential antiviral immunity to Japanese encephalitis virus in developing cortical organoids

Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) poses a serious threat to the world's public health yet without a cure. Certain JEV-infected neural cells express a subset of previously identified intrinsic antiviral interferon stimulated genes (ISGs), indicating brain cells retain autonomous antiviral immunity. However, whether this happens in composited brain remains unclear. Human pluripotent stem cell (hPSC)-derived organoids can model disorders caused by human endemic pathogens such as Zika virus, which may potentially address this question and facilitate the discovery of a cure for JE. We thus generated telencephalon organoid and infected them with JEV. We found JEV infection caused significant decline of cell proliferation and increase of cell death in brain organoid, resulting in smaller organoid spheres. JEV tended to infect astrocytes and neural progenitors, especially the population representing outer radial glial cells (oRGCs) of dev…

Virus-like particles and enterovirus antigen found in the brainstem neurons of #Parkinson's disease

Background: In a previous study on encephalitis lethargica, we identified a virus related to enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed.  Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson's disease (PD) brainstem neurons. Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study. The brain tissue was processed for TEM and IHC according to previous published methods. Results:  We observed VLP in the brainstem neurons of all the cases of PD that were examined.  In the neurons' cytoplasm there were many virus factories consisting of VLP and endoplasmic reticulum membranes. In some neurons, the virus factories contained incomplete VLP. Complete VLP in some neurons' virus factories had an average diameter of 31 n…

Herpes Virus Encephalitis in Adults: Current Knowledge and Old Myths

Herpes simplex virus (HSV) encephalitis is uncommon in clinical practice, but is frequently suspected in patients with acute alterations of consciousness. Symptoms and physical signs are nonspecific, and diagnostic confirmation typically hinges on demonstration of viral DNA in cerebrospinal fluid.BrainMRI is helpful in diagnosis and provides prognostic information. Early initiation of intravenous acyclovir is essential to optimize the patient's chances of favorable recovery. HSV encephalitis can trigger an autoimmune reaction with the possible appearance of antibodies to neuronal surface antigens. Thus, recrudescence of neurologic impairment after a treated episode of HSV encephalitis warrants consideration of secondary autoimmune encephalitis. REFERENCE: Rabinstein AA. Herpes Virus Encephalitis in Adults: Current Knowledge and Old Myths. Neurol Clin. 2017 Nov;35(4):695-705. doi: 10.1016/j.ncl.2017.06.006. Epub 2017 Aug 10. Review. PubMed PMID: 28962808.

The dynamic blood–brain barrier

With the endothelium as its central unit, theblood-brain barrier(BBB) is a complex multicellular structure separating the central nervous system (CNS) from the systemic circulation. Disruption of the BBB has now been implicated in a multitude of acute and chronic CNS disorders indicating the potentially devastating effects of BBB breakdown onbrainfunction. However, the healthy BBB is not an impermeable wall, but rather a communication 'centre', responding to and passing signals between the CNS andblood. New studies are identifying BBB-specific transport pathways that tightly regulate the entry and exit of molecules to and from thebrain. They are revealing a highly plasticbarrierin which dynamic changes in BBB components like paracellular tight junction complexes can contribute to BBB maintenance. Here, we provide a succinct overview of the current state-of-play in BBB research and summarize novel findings into BBB regulation in homeostatic regulation of thebrain. REFERENCE: Ke…

The blood-brain barrier

Bloodvessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. Thebloodvessels that vascularize the central nervous system (CNS) possess unique properties, termed theblood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between thebloodand thebrain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of thesebarrierproperties are an important component of pathology and progression of different neurological diseases. The physiologicalbarrieris coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of thebloodvessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate thebarrierproper…