Novel Synthetic and Natural Therapies for Traumatic Brain Injury

Abstract

: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

Cellular and molecular mechanisms in vascular repair after traumatic brain injury: a narrative review

“…Besides fluid biomarkers, vascular injury, microhemorrhages, CBF changes and BBB impairment can be indicated by neuroimaging biomarkers, such as functional MRI, arterial spin labeling, susceptibility weighted imaging, quantitative susceptibility mapping and contrast-enhanced imaging of MRI techniques [ 244 ]. For more information about biomarkers of TBI and vascular-directed therapeutic strategies, readers are encouraged to refer to recent reviews [ 8 , 244 , 245 ].…”

Credibility of the Neutrophil-to-Lymphocyte Count Ratio in Severe Traumatic Brain Injury

“…BBB breakdown; apoptosis angiogenesis Recombinant human IL-1Ra, NLRP3 inhibitor, Mesenchymal stem/stromal cells therapy, ketamine [18][19][20] Under the pathological conditions of brain trauma, the number of neutrophils entering into the brain increases. Neutrophils are one of the earliest myeloid-derived cells that infiltrate the injured brain and affect secondary damage [36].…”

The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications

“…Utilizing substances with antioxidant properties can decelerate the degeneration of the brain and influence the outcome or the intensity of the complications. Increasing evidence suggests that neuroinflammation and oxidative stress play a significant role in contributing to neurological impairments and the development of posttraumatic epileptogenesis, in addition to cytotoxicity and damage to neurons and glial cells ( Shin et al, 2011 ; Battaglini et al, 2021 ; Fatima et al, 2022a ; Fatima et al, 2022b ; Alam S. et al, 2022d ; Anwar et al, 2023 ).…”