title: Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage.
abstract: Symptomatic ischemia following aneurysmal subarachnoid hemorrhage (SAH) is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits, and vasospasm have focused on the interaction of the "spasmogen" of the extravasated blood with the smooth muscle and endothelium of the arteries. This has led to a comparative neglect of the contribution of the CNS to the maintenance of cerebral perfusion. In the present study, we focused on the role of the rostral ventromedial medulla (RVM) in modulating cerebral perfusion at rest and following an experimental SAH in the rat. Changes in cerebral blood flow (CBF) were measured using laser-Doppler flowmetry and three-dimensional optical microangiography. Focal application of a GABA(A) receptor agonist and antagonist was used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade SAH. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239-3098, USA. cetasj@ohsu.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Cetas
authors.forename: D R
authors.initials: DR
authors.lastname: Lee
authors.forename: N J
authors.initials: NJ
authors.lastname: Alkayed
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: Iliff
authors.forename: M M
authors.initials: MM
authors.lastname: Heinricher
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D021621:Imaging, Three-Dimensional; D017078:Laser-Doppler Flowmetry; D008297:Male; D008526:Medulla Oblongata / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000503:physiopathology; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000503:physiopathology*; D020301:Vasospasm, Intracranial / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D009118:Muscimol; D001640:Bicuculline