Acute Traumatic Brain Injury-Induced Neuroinflammatory Response and Neurovascular Disorders in the Brain

Abstract

Acute traumatic brain injury (TBI) leads to neuroinflammation, neurodegeneration, cognitive decline, psychological disorders, increased blood-brain barrier (BBB) permeability, and microvascular damage in the brain. Inflammatory mediators secreted from activated glial cells, neurons, and mast cells are implicated in the pathogenesis of TBI through secondary brain damage. Abnormalities or damage to the neurovascular unit is the indication of secondary injuries in the brain after TBI. However, the precise mechanisms of molecular and ultrastructural neurovascular alterations involved in the pathogenesis of acute TBI are not yet clearly understood. Moreover, currently, there are no precision-targeted effective treatment options to prevent the sequelae of TBI. In this study, mice were subjected to closed head weight-drop-induced acute TBI and evaluated neuroinflammatory and neurovascular alterations in the brain by immunofluorescence staining or quantitation by enzyme-linked immunosorbent assay (ELISA) procedure. Mast cell stabilizer drug cromolyn was administered to inhibit the neuroinflammatory response of TBI. Results indicate decreased level of pericyte marker platelet-derived growth factor receptor-beta (PDGFR-β) and BBB-associated tight junction proteins junctional adhesion molecule-A (JAM-A) and zonula occludens-1 (ZO-1) in the brains 7 days after weight-drop-induced acute TBI as compared with the brains from sham control mice indicating acute TBI-associated BBB/ tight junction protein disruption. Further, the administration of cromolyn drug significantly inhibited acute TBI-associated decrease of PDGFR-β, JAM-A, and ZO-1 in the brain. These findings suggest that acute TBI causes BBB/tight junction damage and that cromolyn administration could protect this acute TBI-induced brain damage as well as its long-time consequences.

Microenvironmental Variations After Blood-Brain Barrier Breakdown in Traumatic Brain Injury

“…For BBB structures damage, an inevitable consequence of BBB breakdown is an increase in the permeability of the damaged endothelium (Bhowmick et al, 2019). Following TBI, the endothelium-associated tight junction proteins JAM-A, ZO-1, occludin, and claudin-5 were down-regulated indicating acute TBI-associated tight junction protein disruption (Evran et al, 2020;Sivandzade et al, 2020;Kempuraj et al, 2021). The studies showed that after animal TBI model, as many as 40% of the pericytes loss the contact of basement membrane within the first hours of the injury (Dore-Duffy et al, 2000).…”

Severe Suicidality in Athletes with Chronic Traumatic Encephalopathy: A Case Series and Overview on Putative Ethiopathogenetic Mechanisms

“…Such inflammatory milieu might potentiate the risk for SI and SB as they have been convincingly shown to be positive correlates of suicidality [58,59]. In this regard, patients with SA exhibit high levels of several inflammatory markers, such as IL-6 and TNF-α [60,61], all of which were found to be elevated in the cerebrospinal fluid of subjects with traumatic brain injuries [57,62]. Chronic progressive head traumas cause axonal damage resulting in pathogenic expression of tau and TAR DNA binding protein 43 (TDP43) proteins and induction of other factors such as neurofilament light polypeptide (NFL), brain-derived neurotrophic factor (BDNF), and serotonin transporter 5-HTTLPR.…”

CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock

“…A major consequence of TBI is direct damage to the cerebral vasculature, leading to hemorrhage, CBF abnormalities, blood–brain barrier (BBB) disruption, and edema 10 – 12 . These early events are followed by hypoperfusion and compromise of the cerebral microvasculature resulting in capillary stasis, ischemia and hypoxic tissue damage.…”