Assessment of vascular reactivity in rat brain glioma by measuring regional blood volume during graded hypoxic hypoxia

Abstract

While morphological and molecular events during angiogenesis in brain glioma have been extensively studied, the functional properties of tumour vessels have yet received little attention. We have determined changes in regional blood volume (BV) during graded hypoxic hypoxia using susceptibility contrast magnetic resonance imaging in a model of rat brain glioma. Nine anaesthetised and ventilated rats with C6 glioma were subjected to incremental reduction in the fraction of inspired oxygen (FiO 2 ): 0.35, 0.25, 0.15, 0.12, 0.10 and reoxygenation to 0.35. At each episode, BV was determined in peritumoral, intratumoral and contralateral regions. Baseline BV values (FiO 2 of 0.35) were higher in peritumoral than in the contralateral and intratumoral regions. Progressive hypoxia resulted in a graded increase in BV in contralateral and peritumoral regions. At FiO 2 of 0.10, BV increases were comparable between these two regions: 49722% (s.d.) and 28717% with respect of control values, respectively. These BV changes reversed during the reoxygenation episode. By contrast, the intratumoral region had a significant increase in BV at FiO 2 of 0.10 only, with no evidence of return to the basal value during reoxygenation. Immunohistochemical staining of a-smooth muscle actin confirmed reactivity of vessels in the peritumoral region. Our findings indicate that peritumoral vessels present a vascular reactivity to hypoxia, which is comparable to that of nontumoral vessels. A method is thus available for noninvasively demonstrating whether any particular vascular modifying strategy results in the desired outcome in terms of tumour blood volume changes.

Spatial profiles of markers of glycolysis, mitochondria, and proton pumps in a rat glioma suggest coordinated programming for proliferation

“…The rat glioma model was prepared as described [58]: male Wistar rats (200–230 g) were anesthetized with isoflurane and 10 5 C6 cells in DMEM were injected stereotaxically in the right caudate nucleus. The growth of the tumor was monitored by MRI under isofluorane anesthesia at 4.7 T (Avance III console; Bruker, Grenoble MRI Facility IRMaGe) using a T2-weighted sequence (TR/TE = 4,000/33 ms, with repetition time 4,000 ms, and echo time 33 ms [59]).…”

Serial In vivo Spectroscopic Nuclear Magnetic Resonance Imaging of Lactate and Extracellular pH in Rat Gliomas Shows Redistribution of Protons Away from Sites of Glycolysis

“…C6 cells (34) from the American Type Culture Collection were grown in DMEM containing 25 mmol/L glucose and 2 mmol/L glutamine (product 31966-021 from Invitrogen) to which was added 10% FBS (Invitrogen) and antibiotics. Male Wistar rats (200-230 g) were anesthetized with chloral hydrate (400 mg/kg), and 10 5 C6 cells in DMEM were injected stereotaxically in the right caudate nucleus (35). Nuclear magnetic resonance (NMR) experiments were done f25 days after tumor implantation, by which time the rats weighed 275 to 380 g.…”

Measuring Hemoglobin Oxygen Saturation During Graded Hypoxic Hypoxia in Rat Striatum

“…This increase is attributable to the dilation of cerebral arterioles, resulting in increased cerebral blood volume (CBV) (18). We previously measured local changes in CBV (corpus striatum, neocortex, cerebellum) using susceptibility contrast magnetic resonance imaging during experimental conditions similar to those applied in this study (19,20). With the use of indocyanine green and O 2 as intravascular tracers, NIRS has been also proposed to measure CBV and CBF (5).…”