Letter to the Editor Stroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited.
Letter by Shang Regarding Article, “Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation”
To the Editor: The recent publication by Hamner and Tan, titled Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation,1 was of great interest to our group. They analyzed the relationship between specific physiological mechanisms of autoregulation and the overall cerebral pressure–flow relationship. Using projection pursuit regression analysis and ANCOVA decomposition, they were able to analyze the relative contribution of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation, which accounted for 62% of the total cerebral pressure–flow relationship. However, 38% of the cerebral pressure–flow relationship was unexplained. The possible contribution of intrinsic mechanical vessel properties to the cerebral pressure–flow relationship was investigated by testing the pressure–flow relationship on human brachial artery after blockage of sympathetic control. They found that the pressure–flow relationship was mostly linear. Similar linear responses were observed in study of denervated animal middle cerebral artery. Thus, the authors concluded that the intrinsic resistance artery properties could not explain the remaining nonlinearity in the pressure–flow relationship, and therefore could not contribute the 38% of unexplained cerebral autoregulation. The authors should be congratulated for their great effort in elucidating the complex cerebral autoregulation process. Cerebral autoregulation not only involves multiple systems, including neurogenic, myogenic, and metabolic mechanisms, but also develops segmental regulation pathways.2,3 One of the manifestations of cerebral autoregulation complexity is the varied neurogenic reactivity because cerebral vessels branch down from the pial artery to parenchymal artery.2,3 Both the pial artery and the parenchymal artery contribute almost equally to the cerebral vascular resistance system, and thus, cerebral autoregulation. However, there are fundamental differences between the pial artery and the parenchymal artery. The pial artery receives perivascular innervation from peripheral nervous system, such as superior cervical ganglion and trigeminal ganglion (extrinsic innervation). However, the parenchymal artery is innervated by nerve afferents from subcortical neurons, such as locus coeruleus and raphe nucleus (intrinsic innervation).2,3 Furthermore, there is heterogeneity in neurogenic reactivity in the pial and parenchymal arteries. The α-adrenoceptor reactivity is absent in the parenchymal artery because of a shift in the expression of α- to β-adrenoceptor receptor.4 Similar heterogeneity has been shown with the serotonin receptor.4 For example, some neurotransmitters (serotonin
and norepinephrine) have a marked constrictive effect on the large cerebral pial artery but not on the parenchymal artery. In contrast, these neurotransmitters either have no effect on or dilate the parenchymal artery.4,5 Another interesting characteristic of the cerebral parenchymal artery is that it possesses greater basal tone when compared with the pial artery.5 Under this basal tone, pressure-induced myogenic reactivity in parenchymal artery is minimal when compared with corresponding changes in the pial artery.5 In sum, these findings suggest that the parenchymal artery may have additional or different mechanisms, when compared with the pial artery, in regulating cerebral autoregulation. Considering the anatomic and functional differences between the intracranial and the extracranial artery, between the pial and the parenchymal artery, current data from human brachial artery and animal middle cerebral artery may not be readily applicable to the parenchymal artery. The nonlinear pressure–flow relationship may exist in the parenchymal artery because of its unique intrinsic property and its interaction with regulatory mechanisms. In addition to the mechanisms discussed extensively in the study, other important and recognized mechanisms in cerebral autoregulation include metabolic and monoaminergic mechanisms. Particularly, it is reasonable to postulate the critical role of a serotonergic mechanism in cerebral autoregulation, considering the broad distribution of serotonin receptors and its potent function on vascular reactivity in intracranial arteries. Thus, it is possible that the intrinsic reactivity of the parenchymal artery could contribute to the unexplained 38% of cerebral autoregulation. More research is required for a reliable analysis of the complex mechanisms of cerebral autoregulation.
Disclosures None.
Ty Shang, MD, PhD Department of Neurology and Neurotherapeutics University of Texas Southwestern Medical Center Dallas 1. Hamner JW, Tan CO. Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation. Stroke. 2014;45:1771–1777. doi: 10.1161/STROKEAHA.114.005293. 2. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5:347–360. 3. Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol (1985). 2006;100:1059–1064. 4. Lincoln J. Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline. Pharmacol Ther. 1995;68:473–501. 5. Cipolla MJ, Li Rui, Vitullo L. Perivascular innervation of penetrating brain parenchymal arterioles. J Cardiovasc Pharm. 2004;44:1–8.
(Stroke. 2014;45:e208.) © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.114.006566
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on July 24, 2015 e208
Letter by Shang Regarding Article, ''Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation'' Ty Shang Stroke. 2014;45:e208; originally published online August 12, 2014; doi: 10.1161/STROKEAHA.114.006566 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/45/10/e208
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on July 24, 2015
Letter by Shang Regarding Article, “Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation”
To the Editor: The recent publication by Hamner and Tan, titled Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation,1 was of great interest to our group. They analyzed the relationship between specific physiological mechanisms of autoregulation and the overall cerebral pressure–flow relationship. Using projection pursuit regression analysis and ANCOVA decomposition, they were able to analyze the relative contribution of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation, which accounted for 62% of the total cerebral pressure–flow relationship. However, 38% of the cerebral pressure–flow relationship was unexplained. The possible contribution of intrinsic mechanical vessel properties to the cerebral pressure–flow relationship was investigated by testing the pressure–flow relationship on human brachial artery after blockage of sympathetic control. They found that the pressure–flow relationship was mostly linear. Similar linear responses were observed in study of denervated animal middle cerebral artery. Thus, the authors concluded that the intrinsic resistance artery properties could not explain the remaining nonlinearity in the pressure–flow relationship, and therefore could not contribute the 38% of unexplained cerebral autoregulation. The authors should be congratulated for their great effort in elucidating the complex cerebral autoregulation process. Cerebral autoregulation not only involves multiple systems, including neurogenic, myogenic, and metabolic mechanisms, but also develops segmental regulation pathways.2,3 One of the manifestations of cerebral autoregulation complexity is the varied neurogenic reactivity because cerebral vessels branch down from the pial artery to parenchymal artery.2,3 Both the pial artery and the parenchymal artery contribute almost equally to the cerebral vascular resistance system, and thus, cerebral autoregulation. However, there are fundamental differences between the pial artery and the parenchymal artery. The pial artery receives perivascular innervation from peripheral nervous system, such as superior cervical ganglion and trigeminal ganglion (extrinsic innervation). However, the parenchymal artery is innervated by nerve afferents from subcortical neurons, such as locus coeruleus and raphe nucleus (intrinsic innervation).2,3 Furthermore, there is heterogeneity in neurogenic reactivity in the pial and parenchymal arteries. The α-adrenoceptor reactivity is absent in the parenchymal artery because of a shift in the expression of α- to β-adrenoceptor receptor.4 Similar heterogeneity has been shown with the serotonin receptor.4 For example, some neurotransmitters (serotonin
and norepinephrine) have a marked constrictive effect on the large cerebral pial artery but not on the parenchymal artery. In contrast, these neurotransmitters either have no effect on or dilate the parenchymal artery.4,5 Another interesting characteristic of the cerebral parenchymal artery is that it possesses greater basal tone when compared with the pial artery.5 Under this basal tone, pressure-induced myogenic reactivity in parenchymal artery is minimal when compared with corresponding changes in the pial artery.5 In sum, these findings suggest that the parenchymal artery may have additional or different mechanisms, when compared with the pial artery, in regulating cerebral autoregulation. Considering the anatomic and functional differences between the intracranial and the extracranial artery, between the pial and the parenchymal artery, current data from human brachial artery and animal middle cerebral artery may not be readily applicable to the parenchymal artery. The nonlinear pressure–flow relationship may exist in the parenchymal artery because of its unique intrinsic property and its interaction with regulatory mechanisms. In addition to the mechanisms discussed extensively in the study, other important and recognized mechanisms in cerebral autoregulation include metabolic and monoaminergic mechanisms. Particularly, it is reasonable to postulate the critical role of a serotonergic mechanism in cerebral autoregulation, considering the broad distribution of serotonin receptors and its potent function on vascular reactivity in intracranial arteries. Thus, it is possible that the intrinsic reactivity of the parenchymal artery could contribute to the unexplained 38% of cerebral autoregulation. More research is required for a reliable analysis of the complex mechanisms of cerebral autoregulation.
Disclosures None.
Ty Shang, MD, PhD Department of Neurology and Neurotherapeutics University of Texas Southwestern Medical Center Dallas 1. Hamner JW, Tan CO. Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation. Stroke. 2014;45:1771–1777. doi: 10.1161/STROKEAHA.114.005293. 2. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5:347–360. 3. Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol (1985). 2006;100:1059–1064. 4. Lincoln J. Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline. Pharmacol Ther. 1995;68:473–501. 5. Cipolla MJ, Li Rui, Vitullo L. Perivascular innervation of penetrating brain parenchymal arterioles. J Cardiovasc Pharm. 2004;44:1–8.
(Stroke. 2014;45:e208.) © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.114.006566
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on July 24, 2015 e208
Letter by Shang Regarding Article, ''Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation'' Ty Shang Stroke. 2014;45:e208; originally published online August 12, 2014; doi: 10.1161/STROKEAHA.114.006566 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/45/10/e208
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on July 24, 2015
