Endothelin, Cerebral Blood Flow, and Traumatic Brain Injury: Implications for a Future Therapeutic Target
- PMID: 26269891
- Bookshelf ID: NBK299188
Endothelin, Cerebral Blood Flow, and Traumatic Brain Injury: Implications for a Future Therapeutic Target
Excerpt
An early event in the pathotrajectory of traumatic brain injury (TBI) is reduction in cerebral blood flow (CBF). This decrease in CBF likely inhibits the brain’s ability to recover following injury. Until recently, mechanisms underlying dysfunctional CBF have been unknown. However, recent research implicates the endothelin system. Endothelin, working through its receptor A (ETrA), exerts a prolonged period of vaso-constriction throughout brain tissue and contributes to vasospasm. This chapter will not only elucidate the mechanisms by which endothelin affects CBF and ultimate outcome following TBI, but will also offer insight into developments in treatments centered around antagonizing ETrA. It is the hope that this work will inspire future research into pharmacological therapeutics aimed at mitigating the devastating effects of TBI.
© 2015 by Taylor & Francis Group, LLC.
Sections
- 37.1. INTRODUCTION
- 37.2. UNDERSTANDING CBF, ITS REGULATION, AND ITS IMPORTANCE TO OUTCOME
- 37.3. THE ROLE OF ENDOTHELIN IN AUTOREGULATION
- 37.4. THE ROLE OF ENDOTHELIN IN DYSFUNCTIONAL AUTOREGULATION AFTER TBI
- 37.5. THE ROLE OF ENDOTHELIN RECEPTORS IN DYSFUNCTIONAL CBF AFTER TBI
- 37.6. ETA: A THERAPEUTIC TARGET FOR MITIGATING THE DELETERIOUS EFFECTS OF TBI
- 37.7. CONCLUSION
- REFERENCES
References
-
- Armstead W.M. Endothelins and the role of endothelin antagonists in the management of posttraumatic vasospasm. Current Pharmaceutical Design. 2004;10:2185–2192. - PubMed
-
- Armstead W.M, Vavilala M.S. Age and sex differences in cerebral blood flow and autoregulation after pediatric traumatic brain injury. In: Kreipke C.W, Rafols J.A, editors. Cerebral Blood Flow, Metabolism, and Head Trauma. Springer; New York: 2013. pp. 135–153. In.
-
- Armstead W.M, Kreipke C.W. Endothelin-1 is upregulated after traumatic brain injury: A cross-species, cross-model analysis. Neurological Research. 2011;33:133–136. - PubMed
-
- Barone F.C, Ohlstein E.H, Hunter A.J, Campbell C.A, Hadingham S.H, Parsons A.A et al. Selective antagonism of endothelin-A-receptors improves outcome in both head trauma and focal stroke in rat. Journal of Cardiovascular Pharmacology. 2000;36:S357–361. - PubMed
-
- Betrus C, Kreipke C.W. Historical perspectives in understanding traumatic brain injury and in situating disruption in CBF in the pathotrajectory of head trauma. In: Kreipke C.W, Rafols J.A, editors. Cerebral Blood Flow, Metabolism, and Head Trauma. Springer; New York: 2013. pp. 135–153. In.
Publication types
LinkOut - more resources
Full Text Sources