Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets

Abstract

Traumatic brain injury (TBI) causes brain damage, which involves primary and secondary injury mechanisms. Primary injury causes local brain damage, while secondary damage begins with inflammatory activity followed by disruption of the blood–brain barrier (BBB), peripheral blood cells infiltration, brain edema, and the discharge of numerous immune mediators including chemotactic factors and interleukins. TBI alters molecular signaling, cell structures, and functions. Besides tissue damage such as axonal damage, contusions, and hemorrhage, TBI in general interrupts brain physiology including cognition, decision-making, memory, attention, and speech capability. Regardless of the deep understanding of the pathophysiology of TBI, the underlying mechanisms still need to be assessed with a desired therapeutic agent to control the consequences of TBI. The current review gives a brief outline of the pathophysiological mechanism of TBI and various biochemical pathways involved in brain injury, pharmacological treatment approaches, and novel targets for therapy.

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.

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Conceptualization: Conceived and designed the experiments: Thakur Gurjeet Singh. Analyzed the data: Komal Thapa, Thakur Gurjeet Singh. Wrote the manuscript: Komal Thapa and Heena Khan. Editing of the Manuscript: Heena Khan, Amarjot Kaur Grewal. Critically reviewed the article: Thakur Gurjeet Singh.

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Thapa, K., Khan, H., Singh, T.G. et al. Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets. J Mol Neurosci (2021). https://doi.org/10.1007/s12031-021-01841-7

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Keywords

  • Traumatic brain injury
  • Excitotoxicity
  • Mitochondrial dysfunction
  • Oxidative stress
  • Neuroinflammation
  • Apoptosis
  • Nuclear factor-kappa B (NF-κB)