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IGF-1 Deficiency Impairs Cerebral Myogenic Autoregulation in Hypertensive Mice
Abstract
Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice ( Igf1 f/f +TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.
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“GH and IGF-1 receptors are abundantly present throughout the central nervous system (CNS), mediating a range of critical functions. These include regulating endothelial function and vascular reactivity, ensuring proper neurovascular coupling (Toth et al., 2022) and autoregulation (Toth et al., 2014), and facilitating repair mechanisms.”
From Acute neuroendocrine changes after traumatic brain injury (2024) · cites this paper as Toth et al., 2014
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Ungvari, Z., Tarantini, S., Donato, A. J., Galvan, V., & Csiszar, A. (2018) · Circulation Research · doi:10.1161/circresaha.118.311378 · Cited by 919
Self-citationHypertension-induced cognitive impairment: From pathophysiology to public health
Ungvari, Z., Toth, P., Tarantini, S., Prodan, C. I., Sorond, F., Merkely, B., & Csiszar, A. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-021-00430-6 · Cited by 544
Self-citationToth, P., Tarantini, S., Csiszar, A., & Ungvari, Z. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00581.2016 · Cited by 522
Self-citationKiss, T., Nyúl-Tóth, Á., Balasubramanian, P., Tarantini, S., Ahire, C., DelFavero, J., Yabluchanskiy, A., Csipo, T., Farkas, E., Wiley, G., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00177-1 · Cited by 203
Self-citationInvolvement of Bone Marrow Cells and Neuroinflammation in Hypertension
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Self-citationCsiszar, A., Tarantini, S., Fülöp, G. A., Kiss, T., Valcarcel-Ares, M. N., Galvan, V., Ungvari, Z., & Yabluchanskiy, A. (2017) · GeroScience · doi:10.1007/s11357-017-9991-9 · Cited by 93
Self-citationAcute neuroendocrine changes after traumatic brain injury
Magyar-Sumegi, Z. D., Stankovics, L., Lendvai-Emmert, D., Czigler, A., Hegedus, E., Csendes, M., Toth, L., Ungvari, Z., Buki, A., & Toth, P. (2024) · Brain and Spine · doi:10.1016/j.bas.2024.102830 · Cited by 23
Self-citationAge-Related Alterations of Cerebral Autoregulation
Ungvari, A., Kállai, A., Stankovics, L., Lendvai-Emmert, D., Gulej, R., Pal, E., Patai, R., Csik, B., Fekete, M., Lipecz, Á., et al. (2025) · Life · doi:10.3390/life15111669 · Cited by 14
Metadata
- Authors
- Toth, P., Tucsek, Z., Tarantini, S., Sosnowska, D., Gautam, T., Mitschelen, M., Koller, A., Sonntag, W. E., Csiszar, A., & Ungvari, Z.
- Affiliations
- Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
- Department of Pathophysiology and Gerontology, Medical School and Szentagothai Research Center, University of Pecs, Pecs, Hungary
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2014-09-24
- Volume
- 34
- Issue
- 12
- Pages
- 1887-1897
- ISSN
- 0271-678X
- 1559-7016
- Cited by
- 114
- References
- 5
- Language
- en
- Licence
- journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
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