title: 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.
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Annelise
authors.initials: A
authors.lastname: Letourneur
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Roussel
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fillesoye
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Eric T
authors.initials: ET
authors.lastname: MacKenzie
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Petit
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Touzani
authors.affiliation: CNRS, UMR 6301 ISTCT, CEA, Université de Caen Basse-Normandie 'Imaging and Therapeutical Strategies in Cerebral and Tumoral Pathologies'; CERVOxy team, GIP 'Hypoxia, Cerebrovascular and Tumoral Pathophysiologies' CYCERON, Caen, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, Caen, France.|Université de Caen Basse-Normandie, Caen, France.|Normandie Univ, Caen, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Valable
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D001835:Body Weight; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D005909:Glioblastoma / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D006973:Hypertension / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D011897:Random Allocation; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY