Cerebrovascular consequences of common carotid artery thrombosis
Date of Award
Doctor of Philosophy (Ph.D.)
First Committee Member
W. Dalton Dietrich, Committee Chair
Common carotid artery thrombosis (CCAT) leads to hemodynamic changes in the distal cerebral vasculature that may influence the vulnerability of the post-thrombotic brain to future insults. Our objectives were to study the effects of repetitive insults on cerebral infarction following CCAT and to evaluate whether changes in endothelial nitric oxide synthase (eNOS) dependent middle cerebral artery (MCA) dilation may account for the vulnerability patterns following CCAT. Finally, therapeutic strategies directed against the vascular deficits were explored to determine their efficacy. To produce CCAT in male Wistar rats, erythrosin B was injected at 40 mg/kg and the beam of an Argon laser at 514nm was focused on the common carotid artery. To evaluate the presence of ischemic preconditioning induced by CCAT, rats had either sham CCAT + global ischemia, sham global ischemia + CCAT, or CCAT + global ischemia. Rats with CCAT + global ischemia had greater infarction volumes, hemorrhage, and no signs of ischemic preconditioning. To evaluate the more clinically relevant scenario of multiple episodes of embolic stroke, rats had either sham surgery, CCAT, two episodes of CCAT separated by 10 min, 1, 3, 5, or 7 days. To evaluate vascular physiology following CCAT, rats were fitted with a cranial window over the MCA at 6, 24, or 72 hr. The brains were perfusion fixed at 3 days and infarct volumes calculated. Infarction volumes after double CCAT at 1, 3, and 5 days were significantly larger than double COAT at 7 days and single CCAT. eNOS-dependent dilations in rats with cranial window implantation were evaluated by measuring changes in MCA diameter before and after exposure to acetylcholine (Ach). Compared to baseline, there was reduced Ach-induced vascular dilation 6 hrs and greater dilation 24 hrs following CCAT. These results demonstrate an increased vulnerability of the post-thrombotic brain to secondary thrombotic insults. In addition, alterations in eNOS-dependent vascular reactivity after CCAT may participate in the increased vulnerability of the post-thrombotic brain to secondary thrombotic insults. Low doses of the 5HT2 antagonist sarpogrelate was tested for its ability to restore local cerebral blood flow immediately following CCAT. The free radical scavenger polynitroxylated albumin failed to reduce the severe injury following multiple episodes of CCAT suggesting that either free radicals are not required for weakening the vasculature or longer-term therapy is required.
Biology, Neuroscience; Biology, Animal Physiology; Health Sciences, Pathology
Danton, Gary Howard, "Cerebrovascular consequences of common carotid artery thrombosis" (2002). Dissertations from ProQuest. 1884.