Traumatic brain injury (TBI) is a type of acquired injury brought on by a physical blow to the head from the outside that results in brain damage. TBI is a leading cause of death for people of all ages and affects survivors in a variety of short- and long-term ways, with many experiencing significant long-term physical, cognitive, and/or affective deficits and a reduction in quality of life. Additionally, having experienced a TBI is a major non-genetic risk factor for developing neurodegenerative diseases later in life. The recovery process following a TBI cannot currently be improved by any therapy, despite its ubiquity and devastating effects. This is because brain injury is complicated and poorly understood mechanistically.
Autophagy
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Excessive inflammation causes damage
Table of Contents
TBI causes tissue damage and neurological dysfunction both directly (primary injury) and indirectly (secondary injury) by altering cellular and metabolic processes. Neuronal cell death and neuroinflammation are both elements of secondary injury, and they interact and exacerbate one another. Microglia, the native brain immune cells, and myeloid cells, including macrophages and other monocytes, that invade the brain after injury are two cell types that play a role in TBI neuroinflammation-induced disruption to the blood-brain barrier. A typical response to injury in any tissue is the recruitment of activated phagocytic cells, which is crucial for the removal of dead cells, cellular debris, and danger/damage-associated molecular patterns (DAMP). When DAMP is bound and phagocytosed, innate immune responses like the inflammasome and type-I interferon pathways are activated. While these reactions are advantageous in the short term and can facilitate tissue regeneration and healing, excessive or protracted inflammation is harmful and accelerates neurodegenerative processes and neurological dysfunction.
Clinical and experimental findings show that neuroinflammation following brain damage does not go away and can last for decades in TBI patients. Pharmacological treatments that reduce neuroinflammation or eliminate neurotoxic microglia are advantageous for healing after injury, according to numerous studies. The causes of abnormal inflammatory responses following TBI are still not fully understood. An integral component of cellular catabolism, the autophagy-lysosomal pathway facilitates the removal and recycling of damaged proteins, protein aggregates, and organelles. In addition to its well-established function in protein quality control and homeostasis, autophagy is also a key regulator of inflammatory reactions, according to current research. illnesses linked to organs and systemic inflammation, such as inflammatory bowel illnesses, type 2 diabetes, heart conditions, and cystic fibrosis, have been shown to exhibit the interaction between autophagy and inflammation.
Controlled cortical impact (CCI) mouse model research has shown that TBI inhibits autophagy, which in turn causes neuronal cell death in cortical and hippocampus neurons. Additionally, an accumulation of autophagosomes in immune cells that were activated was noticed, pointing to a potential role for autophagy in regulating neuroinflammatory reactions after injury.
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Clinical significance
These findings deepen the understanding of the molecular processes that mediate neuroinflammation following brain damage and hindering its efficient resolution. It also points to autophagy activation as a viable therapeutic strategy for treating injury-related neuronal cell death and neuroinflammation.
Conclusion
Although neuroinflammation plays a significant role in neurotrauma damage, TBI pathology is complicated and also includes other elements like neurodegeneration and demyelination. As a result, addressing several problematic components will be necessary for the creation of an effective treatment.
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