The Role of Neuroinflammatory Mediators in the Pathogenesis of Traumatic Brain Injury: A Narrative Review

Abstract

Traumatic brain injury (TBI) is a debilitating acquired neurological disorder that afflicts nearly 74 million people worldwide annually. TBI has been classified as more than just a single insult because of its associated risk toward various long-term neurological and neurodegenerative disorders. This risk may be triggered by a series of postinjury secondary molecular and cellular pathology, which may be dependent on the severity of the TBI. Among the secondary injury mechanisms, neuroinflammation may be the most crucial as it may exacerbate brain damage and lead to fatal consequences when prolonged. This Review aimed to elucidate the influence of neuroinflammatory mediators on the TBI functional and pathological outcomes, particularly focusing on inflammatory cytokines which were associated with neuronal dysfunctions in the acute and chronic stages of TBI. These cytokines include interleukins (IL) such as IL-1(beta)β, IL-4, IL-6, IL8, IL-10, IL-18, IL-33 and tumor necrosis factor alpha (TNF-α), which have been extensively studied. Apart from these, IL-2, interferon gamma (IFN-γ), and transforming growth factor-beta (TGF-β) may also play a significant role in the pathogenesis of TBI. These neuroinflammatory mediators may trigger a series of pathological events such as cell death, microglial suppression, and increased catecholaminergic activity. Interestingly, in the acute phase of TBI, most of these mediators may also play a neuroprotective role by displaying anti-inflammatory properties, which may convert to a pro-inflammatory action in the chronic stages post TBI. Early identification and treatment of these mediators may help the development of more effective treatment options for TBI.

Expression characteristics of circular RNA in human traumatic brain injury

“…Moreover, microglial cells provide immune responses in respond to a number of stimuli ( 22 ). After TBI, microglia are activated, the activated microglia secrete a large number of neuroimmune inflammatory factors such as interleukin-1β (IL-1β), IL-10 and tumor necrosis factor-α (TNF-α), thus exacerbating the inflammatory response and leading to a series of brain injuries, including cognitive impairment, blood-brain barrier (BBB) disruption and brain edema ( 23 , 24 ). Recently, Eps15, the parent gene of circRNA EPS15, has also been suggested to regulate microglial cell activation and inflammation.…”

“…. thus exacerbating the inflammatory response and leading to a series of brain injuries, including cognitive impairment, blood-brain barrier (BBB) disruption and brain edema (23,24). Recently, Eps15, the parent gene of circRNA EPS15, has also been suggested to regulate microglial cell activation and inflammation.…”

Aβ and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer’s Disease?

“…However, for a more comprehensive understanding of the molecular events triggering Aβ/tau interactions, additional tau's amino acid regions should be considered [178]. In this review, we have extended the discussion by also including those papers describing the cross-relationships between the full-length Aβ peptides and some peptide fragments belonging to N-terminal domain of the tau protein [130,141].…”

Polynitroxylated PEGylated hemoglobin protects pig brain neocortical gray and white matter after traumatic brain injury and hemorrhagic shock

“…Traumatic brain injury (TBI) produces an immediate mechanical injury to brain tissue followed by the secondary injury that evolves over acute, subacute, and chronic stages instigated by imbalances in neurotransmitter signal processing and connectivity, mitochondrial dysfunction, oxidative stress, and neuroinflammation (1)(2)(3)(4)(5). With moderate or severe TBI, early treatment focuses on maintaining mean arterial blood pressure (MABP) and minimizing brain swelling to mitigate intracranial hypertension.…”