Neurovascular Inflammaging in Health and Disease

Abstract

<jats:p>Aging is characterized by a chronic low-grade sterile inflammation dubbed as inflammaging, which in part originates from accumulating cellular debris. These, acting as danger signals with many intrinsic factors such as cytokines, are sensed by a network of pattern recognition receptors and other cognate receptors, leading to the activation of inflammasomes. Due to the inflammasome activity-dependent increase in the levels of pro-inflammatory interleukins (IL-1β, IL-18), inflammation is initiated, resulting in tissue injury in various organs, the brain and the spinal cord included. Similarly, in age-related diseases of the central nervous system (CNS), inflammasome activation is a prominent moment, in which cells of the neurovascular unit occupy a significant position. In this review, we discuss the inflammatory changes in normal aging and summarize the current knowledge on the role of inflammasomes and contributing mechanisms in common CNS diseases, namely Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and stroke, all of which occur more frequently with aging.</jats:p>

Delayed Onset Muscle Soreness (DOMS): The Repeated Bout Effect and Chemotherapy-Induced Axonopathy May Help Explain the Dying-Back Mechanism in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases

“…Recent experimental and clinical observations point towards the fact that inflammation plays a more significant role in ALS pathogenesis [ 31 ]. The vast majority of ALS is late adult-onset, and Mészáros et al [ 32 ] even suggest that neuroinflammation could come earlier than ALS symptoms. Finally, the central nervous system (CNS) involvement is dominant in ALS, while the peripheral nervous system (PNS) involvement is dominant in DOMS.…”

“…The total leukocyte count is elevated in ALS as well [ 42 ], and inflammation is present systemically. It is likely that the low-grade never resolving neuroinflammation of the aging process (inflammaging) [ 32 ], other than ALS associated genetic and environmental factors, further facilitates the degeneration of the peripheral proprioceptive terminals of the muscle spindles [ 43 ] and thus, creating a neuroinflammatory vicious circle in ALS. This non-resolving systemic neuroinflammation and the degeneration of proprioceptive sensory fibers in the presence of environmental and genetic factors lead to the imbalance of microcircuits and eventually a breakaway from homeostasis as suggested by Brownstone et al [ 12 ].…”

Upregulation of Nucleotide-Binding Oligomerization Domain-, LRR- and Pyrin Domain-Containing Protein 3 in Motoneurons Following Peripheral Nerve Injury in Mice

“…In addition, neurons can also express NLRP3 (von Herrmann et al, 2018) to initiate inflammasome formation (Panicker et al, 2020), which is by far the most investigated inflammasome in the CNS. Nowadays it is clear that NLRP3 plays an active role in the pathomechanism of a wide variety of neurological diseases and aging (Latz et al, 2018;Mészáros et al, 2020;Heneka et al, 2013), especially in microglia. Much less is known about regulation of NLRP3 in neurons in response to acute injury.…”

Hypersensitive C-reactive protein-albumin ratio predicts symptomatic intracranial hemorrhage after endovascular therapy in acute ischemic stroke patients

“…It is reported that inflammation may be related to central nervous system diseases, such as stroke, Parkinson’s Disease and Alzheimer disease, and plays a crucial role in the mechanism [ 9 – 12 ]. Gong and his colleagues found the association between high-sensitivity C-reactive protein at admission and progressive motor deficits in patients with penetrating artery infarctions [ 13 ].…”