The cerebral cortex of spontaneously hypertensive rats: A quantitative microanatomical study

The morphology of cerebral cortex was investigated in male spontaneously hypertensive rats (SHR) aged 2, 4 and 6 months (pre-hypertensive, developing hypertension and established hypertension respectively) and in age-matched normotensive Wistar-Kyoto (WKY) rats using quantitative microanatomical techniques. Analysis included frontal and occipital cortex as a paradigm of motor and sensory cerebrocortical areas respectively. Values of systolic pressure were slightly higher in 2-month-old SHR compared to age-matched WKY rats and augmented progressively with increasing age in SHR. In frontal cortex of SHR a decrease of nerve cell number and of cortical volume was observed in layers V and VI of 4- and 6-month-old SHR, and in layers I-IV of 6-month-old SHR. In occipital cortex a decrease of the number of nerve cells and of cortical volume was observed in layers V and VI of 2-, 4-, 6-month-old SHR, and in layers I-IV of 6-month-old SHR. Numerical decrease of neurons in SHR affected to a greater extent occipital cortex than frontal cortex. An increase in the number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes (hyperplasia) as well as in the mean immune reaction area (hypertrophy) was found in the two cerebrocortical areas investigated of 6-month-old SHR. The occurrence of apoptosis and/or necrosis identified using the terminal deoxyribo-nucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) technique was also observed in frontal and occipital cortex of 6-month-old SHR, but not of younger cohorts. These findings indicate the development of microanatomical changes in the cerebral cortex of SHR, the extent of which increases parallel with the progression of hypertension. The occurrence of cerebrocortical apoptosis and/or necrosis as well as the obvious astrogliosis occurring in established hypertension may account for the increased risk of vascular dementia that represents a specific trait of complicated hypertension.