This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coutard, M. Articles by Kontos, H. A. Search for Related Content PubMed PubMed Citation Articles by Coutard, M. Articles by Kontos, H. A. Related Collections Animal models of human disease Acute Cerebral Hemorrhage Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Genetics of Stroke

(Stroke. 2000;31:2678.)
© 2000 American Heart Association, Inc.

Original Contributions

Heritability of Intracerebral Hemorrhagic Lesions and Cerebral Aneurysms in the Rat

Michèle Coutard, PhD; Wei Huang, MD Mary Osborne-Pellegrin, PhD

From Institut National de la Santé et de la Recherche Médicale, Paris, France.

Correspondence to Dr Michèle Coutard, INSERM U 460, IFR Xavier Bichat, 16 rue Henri Huchard, 75870-Paris Cedex 18, France. E-mail coutard{at}bichat.inserm.fr

Background and Purpose—Under certain conditions, the Brown Norway (BN) rat is susceptible to intracerebral hemorrhagic vascular (ICV) lesions within the cerebral cortex, whereas the Long-Evans (LE) rat is prone to develop aneurysms in the circle of Willis. The incidence of these 2 pathological phenotypes was studied in progeny of different BNXLE crosses to determine their heritability in these new rat models. In addition, a possible link between ICV lesion occurrence and either the susceptibility to spontaneous rupture of the arterial internal elastic lamina (IEL) or basal plasma angiotensin-converting enzyme (ACE) activity was also studied in back-cross (BC) F1XBN rats, the only second-generation group with a high incidence of ICV lesions.

Methods—To induce cerebrovascular lesions, rats were submitted to experimental hypertension associated with ligation of 1 carotid artery. After death, the brain was examined for cerebral lesions. Numbers of arterial IEL ruptures were determined microscopically with the use of en face preparations. Plasma ACE activity was determined before the induction of hypertension.

Results—In general, groups that developed ICV lesions presented a low incidence of aneurysms. ICV lesion incidence was similar in F1 hybrids and BC(F1XBN) and greatly decreased in F2 and BC(F1XLE) rats compared with BN rats. No cerebral aneurysms developed in F1 rats. Aneurysmal incidence was 24% (20% ruptured) in LE, 42% (59% ruptured) in F2, and 50% (75% ruptured) in BC(F1XLE) rats. In BC(F1XBN) rats, neither the incidence of IEL rupture nor the plasma ACE activity was higher in the rats with ICV lesions. However, the mean blood pressure level was higher in these rats, and peak blood pressure was higher in rats with the most severe grades of ICV lesions.

Conclusions—These data suggest a polygenic and dominant mode of inheritance of ICV pathology. The formation of aneurysms in the circle of Willis tended to be favored, and their rupture was clearly increased by the presence of BN rat alleles within the LE rat genome. These data may provide the basis for future studies to determine, in new rat models, which genes are involved in these pathologies.

Editorial Comment

Hermes A. Kontos, MD, PhD, Guest Editor

Medical College of Virginia Virginia Commonwealth University Richmond, Virginia

This article has been cited by other articles:

				L. Kota, M. Osborne-Pellegrin, H. Schulz, J. Behmoaras, M. Coutard, M. Gong, and N. Hubner Quantitative genetic basis of arterial phenotypes in the Brown Norway rat Physiol Genomics, June 19, 2007; 30(1): 17 - 25. [Abstract] [Full Text] [PDF]