Heritability of intracerebral hemorrhagic lesions and cerebral aneurysms in the rat.
OBJECTIVE
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.
Coutard
M
M
Institut National de la Santé et de la Recherche Médicale, Paris, France. coutard@bichat.inserm.fr
Huang
W
W
Osborne-Pellegrin
M
M
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000473:pathology; D002941:Circle of Willis / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D002532:Intracranial Aneurysm / Q000235:genetics* / Q000473:pathology; D008297:Male; D051381:Rats / Q000235:genetics; D020318:Rats, Long-Evans / Q000235:genetics