Spontaneously hypertyensive rat (SHR): an animal model of vascular brain disorder

Arterial hypertension is a well-known risk factor for stroke and cognitive deterioration of vascular origin including vascular cognitive impairment (VCI) and vascular dementia (VaD). Patients with ischemic VaD have a significantly greater incidence of hypertension than patients with dementia of the Alzheimer’s type. Areas of white matter hyperintensity and ventricular enlargement are more common in hypertensives subjects compared to normotensive individuals. An association between hypertension and reduced cerebral blood flow and VCI is documented. Hypertension in midlife is associated with a higher probability of cognitive impairment than hypertension developed later in life. These findings collectively indicate that arterial hypertension is a main cause of vascular brain disorder (VBD). In this chapter, the main characteristics of cerebrovascular and brain damage in spontaneously hypertensive rats (SHR) and stroke-prone (SP)-SHR are reviewed. SHR and SHR-SP are two widely used animal models of hypertension and hypertension plus stroke, respectively. They are normotensive at birth and gradually develop severe hypertension in the first 2-4 months of life. At 6 months they have developed a sustained hypertension. SHR were the model most extensively investigated for assessing hypertensive brain damage and treatment of it. The 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, therefore, can represent a reasonable model of morphological damage induced by hypertension and possibly reversed by appropriate antihypertensive treatment. From a neurotransmitter point of view, SHR present changes of some specific neurotransmitter systems that may have functional and behavioral relevance. An impaired cholinergic neurotransmission characterizes both SHR and SHR-SP, similarly as reported in patients affected by VaD The possibility that cholinergic neurotransmission mechanisms contribute to central nervous system plasticity or may improve brain circulation in this animal model is suggested by some studies. SHR are also characterized by a dopaminergic hypofunction and noradrenergic hyperactivity. This causes an imbalance between noradrenergic hyperfunction and dopaminergic hypofunction similarly as occurs in attention-deficit with hyperactivity disorder (ADHD). The majority of microanatomical, behavioral and neurochemical data on SHR are in favor of the hypothesis that this strain is a suitable model of vascular brain disorder. 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, vascular brain disorder 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.