Chronic arterial hypertension impedes glioma growth: a multiparametric MRI study in the rat

Abstract

Glioblastoma is the most aggressive brain tumor and is almost always fatal. These tumors are highly vascularized and angiogenesis is one of the pre-eminent mechanisms underlying their growth. Chronic arterial hypertension (CAH) is a common and worldwide pathology that markedlly alters the structure and function of the vasculature. Yet, essential hypertension is associated in the brain with potential locally impaired vasoreactivity, disturbed perfusion supply and hypoxia phenomena. Even though CAH is a global burden and has an important impact on brain function, nothing is known about the way this frequent pathology would interact with the evolution of glioma. We sought to determine if arterial hypertension influences gliobastoma growth. In the present study, rat glioma C6 tumor cells were implanted in the caudate-putamen of spontaneously hypertensive rats (SHR) or their normotensive controls, the Wistar-Kyoto (WKY) rats. The evolution of the tumor was sequentially analyzed by multiparametric magnetic resonance imaging and the inflammatory response was examined by histochemistry. We found that CAH significantly attenuates the growth of the tumor as, at 21 days, the volume of the tumor was 85.4±34.7 and 126.1±28.8 mm(3), respectively, in hypertensive and normotensive rats (P<0.02). Moreover, cerebral blood volume and cerebral blood flow were greater in the tumors of hypertensive rats (P<0.05). The lesser growth of the tumor observed in normotensive animals was not due to an enhanced rejection of the tumor cells in WKY rats, the inflammatory response being similar in both groups. For the first time, these results show that CAH impedes the growth of glioblastoma and illustrate the need to further study the impact of hypertension on the evolution of brain tumors.

Diffusion kurtosis imaging for characterizing tumor heterogeneity in an intracranial rat glioblastoma model

“…In contrast to our hypothesis, we did not observe any temporal evolution in DKI parameters with tumor growth, as the tumor tissue clearly became more heterogenous with time, with increased necrotic areas. An increase in ADC over time has been reported by Letourneur et al 29 in a rat model with C6 glioma. However, no changes in ADC were observed in F98 tumors 29 or 9 L tumors 41 …”

“…The increased MD may be due to increased extracellular diffusivity, or a significant increase in intracellular water diffusion due to cellular swelling. An increased mean diffusivity in tumors relative to the contralateral cortex was reported in rats with F98 and C6 glioma, 8–10,29 although some discrepancy exists, as another study reported decreased MD in C6 gliomas 30 . MRI diffusion parameters, such as MD and FA, have shown potential for predicting tumor grade, 31,32 treatment monitoring and prognosis 33 .…”

Baseline and longitudinal change in blood pressure and mortality in a Chinese cohort

“…Several mechanisms may explain the inverse associations observed for cancer in our study. In animal models, they observed significant attenuation of tumour growth in spontaneously hypertensive rats 27. The possible reason was partly due to the impaired angiogenesis as a result of chronic hypertension.…”

Associations between prediagnostic blood glucose levels, diabetes, and glioma

“…To the extent that glioblastoma stem cells are related to neural stem cells 41 hyperglycaemia may confer protection against glioblastoma. Another potential mechanism is inhibition of cerebral circulation associated with diabetes 42, 43 causing reduced glioma risk 44 . In addition, lower levels of insulin-like growth factor 1 (IGF-1) are found in diabetic than in non-diabetic serum 45 and tumour-associated macrophage derived IGF-1 may drive glioma recurrence 46 .…”