Reactive gliosis and neuroinflammation: prime suspects in the pathophysiology of post-acute neuroCOVID-19 syndrome

Abstract

IntroductionAs the repercussions from the COVID-19 pandemic continue to unfold, an ever-expanding body of evidence suggests that infection also elicits pathophysiological manifestations within the central nervous system (CNS), known as neurological symptoms of post-acute sequelae of COVID infection (NeuroPASC). Although the neurological impairments and repercussions associated with NeuroPASC have been well described in the literature, its etiology remains to be fully characterized.ObjectivesThis mini-review explores the current literature that elucidates various mechanisms underlining NeuroPASC, its players, and regulators, leading to persistent neuroinflammation of affected individuals. Specifically, we provide some insights into the various roles played by microglial and astroglial cell reactivity in NeuroPASC and how these cell subsets potentially contribute to neurological impairment in response to the direct or indirect mechanisms of CNS injury.DiscussionA better understanding of the mechanisms and biomarkers associated with this maladaptive neuroimmune response will thus provide better diagnostic strategies for NeuroPASC and reveal new potential mechanisms for therapeutic intervention. Altogether, the elucidation of NeuroPASC pathogenesis will improve patient outcomes and mitigate the socioeconomic burden of this syndrome.

Decoding Post-Viral Fatigue: The Basal Ganglia’s Complex Role in Long-COVID

“…As a microtubule inhibitor used to treat gout, colchicine possesses anti-inflammatory properties that appear beneficial in long-COVID. Specifically, by suppressing microglial activation and attendant release of cytokines, like IL-1β, TNF-α, and nitric oxide, colchicine may interrupt self-amplifying cycles of immunemediated dopaminergic injury centered on the basal ganglia [59,60]. Researchers posit that subsequent reductions in aberrant microglial pruning allow recovery of disrupted motivation/reward and motor control pathways [60].…”

Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition

“…Neurological manifestations are major complications of PCC, affecting one-third of patients, with symptoms persisting for more than a month post-COVID-19 infection [33]. According to the above findings, the patients with PCC exhibited a series of symptoms related to reactive gliosis and neuroinflammation in the CNS, including neuropsychiatric manifestations such as fatigue, 'brain fog' (characterized by short-term memory loss and difficulty concentrating), headache, drowsiness, cognitive impairment, sleep disorders, mood changes, disorders of smell or taste, myalgias, anxiety, posttraumatic stress, depression, sleep disturbances, sensorimotor deficits (neuropathy, paresthesia, weakness, and myalgia), and dysautonomia [1,2,[34][35][36][37][38]. Among the PCC symptoms, prolonged cognitive dysfunction is one of the most common impairments affecting between 17 and 28% of the individuals, and in some cases, persisting for several years.…”

Reactive Gliosis in Neonatal Disorders: Friend or Foe for Neuroregeneration?

“…Interestingly, not only a shortage of trophic support but also overnutrition in the postnatal period was postulated to trigger hypothalamus astrogliosis in rat models [121]. Astrogliosis is also a common feature of other neonatal disease conditions like intraventricular hemorrhages in pre-term children [122], neuroinflammation evoked by sepsis [123], hyperbilirubinemia [124], and other intrauterine and postnatal infections (especially in preterm born children), including coronavirus disease 2019 (COVID-19) inflammation [125,126]. In recent studies, SARS-CoV-2 was shown to exhibit tropism towards human cortical astrocytes [127,128].…”