Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

With confirmed coronavirus disease 2019 (COVID-19) cases surpassing the 18 million mark around the globe, there is an imperative need to gain comprehensive understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are associated with respiratory or intestinal symptoms, reports of neurological signs and symptoms are increasing. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the central nervous system (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier.

Detrimental Effects of HMGB-1 Require Microglial-Astroglial Interaction: Implications for the Status Epilepticus -Induced Neuroinflammation.

Temporal Lobe Epilepsy (TLE) is the most common form of human epilepsy and available treatments with antiepileptic drugs are not disease-modifying therapies. The neuroinflammation, neuronal death and exacerbated plasticity that occur during the silent period, following the initial precipitating event (IPE), seem to be crucial for epileptogenesis. Damage Associated Molecular Patterns (DAMP) such as HMGB-1, are released early during this period concomitantly with a phenomenon of reactive gliosis and neurodegeneration.

G5G2.5 core-shell tecto-dendrimer specifically targets reactive glia in brain ischemia.

Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro-inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke.

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy.

The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures.

Toll-Like Receptor 4 (TLR4) and Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2) Activation Balance Astrocyte Polarization into a Proinflammatory Phenotype.

Astrocytes react to brain injury with a generic response known as reactive gliosis, which involves activation of multiple intracellular pathways including several that may be beneficial for neuronal survival. However, by unknown mechanisms, reactive astrocytes can polarize into a proinflammatory phenotype that induces neurodegeneration. In order to study reactive gliosis and astroglial polarization into a proinflammatory phenotype, we used cortical devascularization-induced brain ischemia in Wistar rats and primary astroglial cell cultures exposed to oxygen-glucose deprivation (OGD).

Peripheral Inflammation and Demyelinating Diseases.

In recent decades, several neurodegenerative diseases have been shown to be exacerbated by systemic inflammatory processes. There is a wide range of literature that demonstrates a clear but complex relationship between the central nervous system (CNS) and the immunological system, both under naïve or pathological conditions. In diseased brains, peripheral inflammation can transform "primed" microglia into an "active" state, which can trigger stronger pathological responses.

Isolation and Characterization of Ischemia-Derived Astrocytes (IDAs) with Ability to Transactivate Quiescent Astrocytes.

Unlabelled: Reactive gliosis involving activation and proliferation of astrocytes and microglia, is a widespread but largely complex and graded glial response to brain injury. Astroglial population has a previously underestimated high heterogeneity with cells differing in their morphology, gene expression profile, and response to injury. Here, we identified a subset of reactive astrocytes isolated from brain focal ischemic lesions that show several atypical characteristics.

Chronic systemic IL-1β exacerbates central neuroinflammation independently of the blood-brain barrier integrity.

Peripheral circulating cytokines are involved in immune to brain communication and systemic inflammation is considered a risk factor for flaring up the symptoms in most neurodegenerative diseases. We induced both central inflammatory demyelinating lesion, and systemic inflammation with an interleukin-1β expressing adenovector. The peripheral pro-inflammatory stimulus aggravated the ongoing central lesion independently of the blood-brain barrier (BBB) integrity.

CNS response to a second pro-inflammatory event depends on whether the primary demyelinating lesion is active or resolved.

Interleukin-1β (IL-1β) is considered to be one of the most important mediators in the pathogenesis of inflammatory diseases, particularly in neurodegenerative diseases such as multiple sclerosis (MS). MS is a chronic inflammatory disease characterized by demyelination and remyelination events, with unpredictable relapsing and remitting episodes that seldom worsen MS lesions. We proposed to study the effect of a unique component of the inflammatory process, IL-1β, and evaluate its effect in repeated episodes, similar to the relapsing-remitting MS pathology.

Influence of Peripheral inflammation on the progression of multiple sclerosis: evidence from the clinic and experimental animal models.

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination, remyelination and loss of functions. Even though its etiology is unknown viral, genetic and environmental factors are considered triggers of the disease. MS shows a heterogeneous clinical course, but most patients exhibit exacerbations and remissions from the onset, eventually leading to secondary progressive multiple sclerosis.

The degenerating substantia nigra as a susceptible region for gene transfer-mediated inflammation.

Parkinson's disease (PD) is characterized by the progressive degeneration of neurons in the substantia nigra pars compacta (SN). The naïve SN is highly susceptible to inflammation. In addition, microglial activation in the degenerating SN displays distinct characteristics that increase the reactivity of the region towards inflammatory stimuli.