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- Antihypertensive drug blocks inflammation following TBI
Antihypertensive drug blocks inflammation following TBI
A new animal study shows that traumatic brain injury (TBI) affects the body as well as the brain and that treatment with angiotensin II receptor blocker antihypertensive drugs block the production of mediators of inflammation.
In the study, published online today in The American Journal of Pathology, the Georgetown University Medical Center (GUMC) research team reveals for the first time that experimental traumatic brain injury results in a systemic inflammatory response primarily in the liver. Using a male mouse TBI model of controlled cortical impact injury (CCI), Villapol et al (Am J Pathol 2015, 185:XXXX–XXXX) examined liver and plasma expression of the early APR biomarker serum amyloid A1 (SAA1). Besides the expected immediate up-regulation of SAA1 in the liver in response to CCI, increases in neutrophil and macrophage infiltration, apoptosis, and CXCL1 and CXCL10 chemokine levels were observed.
A delayed increase in the mRNA expression of angiotensin II receptor (AT1R) was also noted. The investigators also discovered that in mice, small doses of telmisartan, an Angiotensin II receptor blocker (collectively called sartans) used in the treatment of hypertension, 1 hour post injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression after 3 days without affecting expression of CXCL1 or the number of apoptotic cells or infiltrating leukocytes. This led the authors to suggest that telmisartan could be therapeutic for blocking the hepatic acute phase response following TBI.
In earlier research, Villapol and her colleagues (Villapol et al., 2015) observed that telmisartan and another hypertension drug, candesartan, when administered six hours after experimental TBI (mice, controlled cortical impact model) had significantly reduced inflammation, neuronal loss, brain swelling and improved cognitive outcome at one month post injury. The six hours time to treatment is very important since it is very realistic in terms of the time frames, treatment can be instituted following traumatic brain injury. The authors are optimistic that these encouraging results will lead for clinical trials of these drugs in traumatic brain injury.
Citation:
- Villapol, S., Balarezo, M. G., Affram, K., Saavedra, J. M., & Symes, A. J. (2015). Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Brain. doi:10.1093/brain/awv172
- Villapol, S., & Saavedra, J. (2015). Neuroprotective effects of angiotensin receptor blockers. American Journal of Hypertension, 28(3), 289–99. doi:10.1093/ajh/hpu197
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