According to research, when the capybara reaches sexual maturity, one of the main arteries that vascularize its brain closes

Scientists propose using the capybara as a natural model in which to study cerebrovascular accident
2014-02-19

According to research, when the capybara reaches sexual maturity, one of the main arteries that vascularize its brain closes.

Scientists propose using the capybara as a natural model in which to study cerebrovascular accident

According to research, when the capybara reaches sexual maturity, one of the main arteries that vascularize its brain closes.

2014-02-19

According to research, when the capybara reaches sexual maturity, one of the main arteries that vascularize its brain closes

 

By Karina Toledo

Agência FAPESP – In addition to being the largest rodent in the world, the capybara (Hydrochoeris hydrochaeris) has another very peculiar anatomical characteristic: when it reaches sexual maturity at approximately one year of age, one of the main arteries that vascularize its brain closes. Simultaneously, another doubles in size and undergoes a process of remodeling to meet the brain’s demand for oxygen and nutrients.

A similar obstructive process that is, however, more sudden and has a potentially more disastrous outcome can occur in humans with atherosclerosis and coagulopathies. Because of this similarity, scientists at the Universidade de São Paulo (USP) and University College London (UCL), have proposed using the capybara as a model to study ischemic cerebrovascular accident (CVA) – caused by the occlusion of a major artery that vascularizes the brain – in an article published in the journal Cells Tissues Organs.

“The capybara would be a better animal model than the rat because it has an average body weight (between 20 kilograms to 40 kilograms) and longevity (from 10 to 14 years) more comparable with the human species. This could be a multidisciplinary area of study with participation in the pharmaceutical industry to test new drugs,” opined veterinarian and professor Augusto Coppi, who is responsible for the Laboratory of Stochastic Stereology and Chemical Anatomy (LSSCA) and USP’s Department of Surgery and School of Veterinary Medicine and Zootechny (FMVZ) and is the coordinator of the FAPESP-funded study.

In humans and capybaras, as well as in other mammals, the two main blood carriers to the brain are the internal carotid artery and the basilar artery. “The carotid arteries begin at the heart and continue up on both sides of the neck, and when they reach the ears split into the external and internal carotid (from which the majority of cerebral arteries originate). The basilar artery is formed by the junction of vertebral arteries at the height of the nape of the neck. This system is also called the vertebral-basilar system,” explained Coppi.

In capybaras, at approximately six months of age, the internal carotid artery naturally begins to undergo a process of fibrosis, and at 12 months, it is completely obstructed by conjunctive tissue, similar to a fibrous string. Concomitantly, the basilar artery undergoes a structural readaptation to become the main supplier of blood to the brain.

“This a physiological process, and we don’t know for certain why this happens. We formulated some hypotheses in previous studies published by our group, and the most probable is that the basilar artery becomes largely responsible for vascularization of the capybara’s entire brain. The internal carotid loses its function after sexual maturation,” explained Coppi.

In humans, however, the internal carotid and basilar arteries share the task of cerebral vascularization. “The internal carotid artery, however, is more prone to being obstructed by atheromatous plaque (formed by cholesterol and calcium) than the basilar. And, unfortunately, unlike the capybaras, the process is sudden, and there is no time for the other system to remodel to supply the brain’s blood needs.”

Nervous impulse

In the study published in the journal Cells Tissues Organs, the researchers analyzed tissue samples of the basilar artery in adult capybaras and the nerves that they involve. “Our objective was to discover how the nerves that supply this artery behave, which are fundamental to guarantee the motility of the vein and consequently the adequate conduction of blood and nutrients for the brain. Simply increasing the artery’s diameter is not enough. If the blood flow is not regular and constant through the vertebral-basilar system, the cerebral tissue could incur lesions,” explained Coppi.

With the aid of immunocytochemical techniques (which use antibodies to identify molecules on a subcellular level), transmission electron microscopy (which allows for visualization of structures at subcellular levels) and stereology (3-D microscopy), the scientists confirmed the existence of synapses and active nerve endings in the remodeled basilar artery; or rather, communication between the nerve fibers and the modified basilar artery in adult capybaras.

They also confirmed the presence of two vasoactive substances (which stimulate vein contraction): endothelin-1 and its receptor, endothelin A.

“Not all veins have endothelin – a very important substance for maintaining cerebral hemodynamism. There are other vasoactive substances, such as noradrenaline, for example, but the endothelin offers more fine-tuned control and regular conduction of the blood. We managed to confirm that after the internal carotid artery closes during puberty, the basilar artery of adult capybaras takes control and doubles in diameter, making it therefore capable of regularly supplying blood to the entire brain,” explained Coppi.

According to the researcher, the presence of endothelin in the basilar artery has already been described both in humans and in rats. However, this is the first time in the medical literature that the existence of this vasoactive substance has been confirmed in the basilar artery (and its associated nerve) in capybaras.

“Future studies could confirm whether there are other vasoactive substances in the basilar artery of capybaras. We also suggested the study of new drugs that can act on this location. The idea is to think of new biochemical markers that can signal and induce rapid and efficient angiogenesis in the carotid system, while at the same time activating the remodeling mechanism of the basilar artery in a similar manner to what we see in capybaras, promoting alternative blood circulation to the brain,” stated Coppi.

The partnership with the researchers at University College London has already spanned more than a decade and has resulted in three publications. In 2004, in the periodical Anatomia, Histologia, Embryologia, the group structurally described the obstruction process of the internal carotid artery and the remodeling of the basilar artery in the capybara.

In 2005, in the Journal of Molecular Histology, the authors discussed the possible presence of endothelin-1 and its receptor in the basilar artery of capybaras.

A study published in 2006 in Cell and Tissue Research described, with a great wealth of details, the structural alterations of the obstructed internal carotid artery and the increase of caliber and structural remodeling of the basilar artery.

“It is a series of studies through which we have been investigating the process in an integrated and multidisciplinary manner, aiming to understand it more profoundly and holistically. In the latest study, we moved to the molecular biology level, and we have robust subsidies to propose the use of this animal as a model for ischemic CVA.”

According to data from the Brazilian Cardiology Society (SBC), CVA is the leading cause of death from circulatory system disorders in Brazil. An estimated 350,000 Brazilians will likely be affected in 2014.

The article Immunoreactive Endothelin-1 and Endothelin A Receptor in Basilar Artery Perivascular Nerves of Young and Adult Capybaras (doi: 10.1159/000348617) can be read at www.karger.com/Article/FullText/348617.

For more information, contact researchers by e-mail at guto@usp.br, visit www.lssca.fmvz.usp.br or LSSCA’s page on Facebook.

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