Reactive gliosis in traumatic brain injury: a comprehensive review

Abstract

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting the central nervous system (CNS). A neurological deficit associated with TBI results from a complex of pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or the development of edema. The critical components contributing to CNS response, damage control, and regeneration after TBI are glial cells–in reaction to tissue damage, their activation, hypertrophy, and proliferation occur, followed by the formation of a glial scar. The glial scar creates a barrier in damaged tissue and helps protect the CNS in the acute phase post-injury. However, this process prevents complete tissue recovery in the late/chronic phase by producing permanent scarring, which significantly impacts brain function. Various glial cell types participate in the scar formation, but this process is mostly attributed to reactive astrocytes and microglia, which play important roles in several brain pathologies. Novel technologies including whole-genome transcriptomic and epigenomic analyses, and unbiased proteomics, show that both astrocytes and microglia represent groups of heterogenic cell subpopulations with different genomic and functional characteristics, that are responsible for their role in neurodegeneration, neuroprotection and regeneration. Depending on the representation of distinct glia subpopulations, the tissue damage as well as the regenerative processes or delayed neurodegeneration after TBI may thus differ in nearby or remote areas or in different brain structures. This review summarizes TBI as a complex process, where the resultant effect is severity-, region- and time-dependent and determined by the model of the CNS injury and the distance of the explored area from the lesion site. Here, we also discuss findings concerning intercellular signaling, long-term impacts of TBI and the possibilities of novel therapeutical approaches. We believe that a comprehensive study with an emphasis on glial cells, involved in tissue post-injury processes, may be helpful for further research of TBI and be the decisive factor when choosing a TBI model.

A Pilot Study on a Possible Mechanism behind Olfactory Dysfunction in Parkinson’s Disease: The Association of TAAR1 Downregulation with Neuronal Loss and Inflammation along Olfactory Pathway

“…Not only did the number of TAAR1 + /GFAP + double positive cells increase (Figure 8I), but the ratio of TAAR1 + /GFAP + cells to TAAR1 + cells also increased (Figure 8J). These results indicated that TAAR1 levels were increased in the astrocytes within the OB and the PC in PD mice, which might modulate the enhancement of neuroinflammation in these regions [48].…”

“…Consequent to these findings, the reduction of TAAR1 along the olfactory pathway in our study might result in Bcl-2/caspase-3 alterations and lead to neuronal damage. (2) Regulating the activity of astrocytes: Activation of TAAR1 in astrocytes significantly downregulates the level of the glutamate transporter EAAT-2, leading to an accumulation of glutamate and subsequent cytotoxicity [39,64] due to the corresponding influx of Ca 2+ into the cells to trigger apoptotic signals and the release of IL-1β, resulting in apoptosis and neuroinflammation [48]. The following two possible mechanisms are speculated according to previous reports and require further investigation: (3) Regulating the activity of microglia: Activation of TAAR1 in microglia can suppress the release of proinflammatory factors such as IL-6, TNF-α, NF-κB, MCP1, and MIP1, while simultaneously promoting the release of anti-inflammatory mediators like IL-10, thus fulfilling an anti-inflammatory role [40].…”

Water channels in the brain and spinal cord—overview of the role of aquaporins in traumatic brain injury and traumatic spinal cord injury

“…Despite ionic accumulation, AQP4 contributes to the cytotoxic and vasogenic edema due to increased expression and translocation from the astrocytic endfeet to the whole astrocyte, thereby causing intracellular fluid accumulation and astrocyte swelling ( Badaut, 2017 ). During TBI, microglia undergo morphological changes and become immunoreactive, which results in release of pro-and anti-inflammatory mediators ( Amlerova et al, 2024 ). This triggers immune cell migration from the periphery to the injury site through the disrupted BBB.…”

“…Alterations in ion transport leads to opening of Ca 2+ channels, which causes further neuron depolarization, ultimately resulting in further glutamate release and intracellular fluid accumulation ( Zusman et al, 2020 ). The intracellular accumulation of Ca 2+ triggers apoptotic signals leading to cell death and release of inflammatory mediators eventually causing inflammation ( Amlerova et al, 2024 ). Neurons and oligodendrocytes are especially susceptible to apoptosis.…”

“…Neurons and oligodendrocytes are especially susceptible to apoptosis. When oligodendrocytes undergo apoptosis, myelin production decreases, causing axonal demyelination ( Amlerova et al, 2024 ). Although demyelination is followed by remyelination, the inflammatory microenvironment and astroglial scar impairs remyelination ( Jarrahi et al, 2020 ).…”