Animal Models of VaD: Any Utility for Clinical Application?

Arterial hypertension is the main risk factor for stroke and plays a role in the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). An association between hypertension and reduced cerebral blood flow and VCI is documented and arterial hypertension in midlife is associated with a higher probability of cognitive impairment. These findings suggest that arterial hypertension is a main cause of vascular brain disorder (VBD). Spontaneously hypertensive rat (SHR) is the rat strain most extensively investigated and used for assessing hypertensive brain damage and treatment of it. They are normotensive at birth and at 6months they have a sustained hypertension. Time-dependent rise of arterial blood pressure, the occurrence of brain atrophy, loss of nerve cells and glial reaction are phenomena shared to some extent with hypertensive brain damage in humans. SHR present changes of some neurotransmitter systems that may have functional and behavioral relevance. An impaired cholinergic neurotransmission characterizes SHR, similarly as reported in patients affected by VaD. SHR are also characterized by a dopaminergic hypofunction and noradrenergic hyperactivity similarly as occurs in attention-deficit with hyperactivity disorder (ADHD). Microanatomical, neurochemical and behavioral data on SHR are in favor of the hypothesis that this strain is a suitable model of VBD. Changes in catecholaminergic transmission put forward SHR as a possible model of ADHD as well. Hence SHR could represent a multi-faced model of two important groups of pathologies, VBD and ADHD. As for most models, researchers should always consider that SHR offer some similarities with corresponding human pathologies, but they do not suffer from the same disease. This paper reviews the main microanatomical, neurochemical and behavioral characteristics of SHR with particular reference as an animal model of brain vascular injury.