1987 Volume 9 Issue 6 Pages 499-507
An unique model, the stroke-prone spontaneously hypertensive rat (SHRSP) developing hemorrhagic or thrombotic stroke spontaneously without exception nowadays, was established by our hands and has been extensively studied not only on the pathogenesis but also prevention of stroke. Moreover, in search of “a model for lacular stroke” which is preponderant cause of cerebrovascular dementia in aged populations such as Japan, we recently succeeded in establishing the model by cross breeding between SHPSP and OM strain with accelerated platelet aggregavility.
Studies on the pathogenesis showed the genetic factors (consisting of more than 5 major genes) and their interaction with environmental, especially nutritional factors such as salt, protein and lipid intakes were important : Cultured smooth muscle cells obtained from SHRSP are more vulnerable to hypoxia than those from normotensive control rats, offering the evidence suggestive of cellular desposition to cerebrovascular damages. Severe hypertension, through cerebral blood flow reduction in the brain region fed by recurrent arteries, induces initially medial necrosis of small intracerebral arteries which is the basic vascular lesions for either cerebral hemorrhage or infarction. Dietary conditions with Na/K ratio accelerate the development of such arterionecrothrombogenic strokes. Not only K but also dietary fibers, especially seaweed or alginic acid obtained from it, counteract the adverse effect of salt and the preventive mechanism of stroke by dietary fibers has been proven to be due to the reduction of gastro-intestinal Na absorption. In contrast, protein-rich diets decrease the incidence of stroke through the attenuation of hypertension, the acceleration of urinary Na excretion and the preservation of vascular wall distensibility. Further, taurine rich in fish protein has been proven to prevent stroke by the neurogenic attenuation of severe hypertension. Among several fatty acids chronically given to SHRSP palmitoleic acid (POA) was proven to be effective for stroke-prevention even in SHRSP on high salt diets.
Some indices such as early development of hypertension, stress-sensitivity, salt-sensitivity tendency toward cardiovascular hypertrophy and biomembrance abnormalities resulting in intracelullar Na retention, are possibly related to predisposition to hypertension and stroke and, may be utilized for the scientific prediction of stroke. Our recent studies indicated vulnerability to hypoxia in SHRSP brain, detected by an abnormal increase in phosphate to phosphocreatine ratio under hypoxia or ischemia by using a 31P-NMR could be used as a clinically available index for predicting the development of stroke in advance. Thus, stroke is experimentally predictable, and evidently preventable by the control of blood pressure, nutritional conditions and also of thrombogenesis.
The most important message obtained from our experimental models of stroke is that “stroke can be prevented by non-pharmacological dietary intervention even in animal models strongly predisposed to cerebrovascular diseases”. Accumulating evidence obtained by our epidemiological and clinical studies support that these experimental findings in animal models can be applied to humans.
