Abstract
BackgroundHypertension is an important risk factor for cerebrovascular disease, including stroke and dementia. Both in humans and animal models of hypertension, neuropathological features such as brain atrophy and oedema have been reported. We hypothesised that cerebrovascular damage resulting from chronic hypertension would manifest itself in a more permeable blood–brain barrier and blood–cerebrospinal fluid barrier. In addition, more leaky barriers could potentially contribute to an enhanced interstitial fluid and cerebrospinal fluid formation, which could, in turn, lead to an elevated intracranial pressure.MethodsTo study this, we monitored intracranial pressure and estimated the cerebrospinal fluid production rate in spontaneously hypertensive (SHR) and normotensive rats (Wistar Kyoto, WKY) at 10 months of age. Blood–brain barrier and blood–cerebrospinal fluid barrier integrity was determined by measuring the leakage of fluorescein from the circulation into the brain and cerebrospinal fluid compartment. Prior to sacrifice, a fluorescently labelled lectin was injected into the bloodstream to visualise the vasculature and subsequently study a number of specific vascular characteristics in six different brain regions.ResultsBlood and brain fluorescein levels were not different between the two strains. However, cerebrospinal fluid fluorescein levels were significantly lower in SHR. This could not be explained by a difference in cerebrospinal fluid turnover, as cerebrospinal fluid production rates were similar in SHR and WKY, but may relate to a larger ventricular volume in the hypertensive strain. Also, intracranial pressure was not different between SHR and WKY. Morphometric analysis of capillary volume fraction, number of branches, capillary diameter, and total length did not reveal differences between SHR and WKY.ConclusionIn conclusion, we found no evidence for blood–brain barrier or blood–cerebrospinal fluid barrier leakage to a small solute, fluorescein, in rats with established hypertension.
Highlights
Hypertension is an important risk factor for cerebrovascular disease, including stroke and dementia
This extra-choroidal secretion is believed to derive from the ependymal epithelium and possibly the interstitial fluid (ISF) formation across the blood–brain barrier (BBB) of cerebral capillaries that subsequently drains into the cerebrospinal fluid (CSF) compartment [8, 9]
CSF glucose levels were remarkably high in both strains, but were significantly lower in spontaneously hypertensive rats (SHR) when compared to Wistar Kyoto rats (WKY) (p ≤ 0.001)
Summary
Hypertension is an important risk factor for cerebrovascular disease, including stroke and dementia. Chronic hypertension is a well-established risk factor for cerebrovascular disease, including haemorrhagic stroke, vascular dementia and Alzheimer’s disease It is associated with alterations in the structure and function of cerebral blood vessels, which may contribute to hypoperfusion, microinfarcts, brain atrophy, oedema, and Dysfunction at the blood–brain barrier (BBB) is often regarded as an early and common denominator in cerebrovascular disease. More recent reports described that the remaining CSF stems from an extra-choroidal source [4,5,6,7] This extra-choroidal secretion is believed to derive from the ependymal epithelium and possibly the ISF formation across the BBB of cerebral capillaries that subsequently drains into the CSF compartment [8, 9]. The exact contribution of extra-choroidal CSF to the total CSF production is still under debate, and may even play a minimal role under physiological circumstances [10]
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