Physical Activity Attenuates Brain Irradiation-Associated Skeletal Muscle Damage in the Rat.

Purpose: Radiation therapy for brain tumors increases patient survival. Nonetheless, side effects are increasingly reported such as cognitive deficits and fatigue. The etiology of fatigue remains poorly described.

Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy.

Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery (tMCAo). By analyzing recently published bulk and single cell RNA sequencing databases, we show that the phagocytosis dysfunction was not explained by transcriptional changes.

Nanosized zeolites as a gas delivery platform in a glioblastoma model.

Approaches able to counteract, at least temporarily, hypoxia, a well-known factor of resistance to treatment in solid tumors are highly desirable. Herein, we report the use of nanosized zeolite crystals as hyperoxic/hypercapnic gas carriers for glioblastoma. First, the non-toxic profile of nanosized zeolite crystals in living animals (mice, rats and non-human primates) and in various cell types is presented.

How to assess and manage cognitive impairment induced by treatments of non-central nervous system cancer.

A number of neurotoxicity associated with oncological treatments has been reported in non-central nervous system cancers. An expert group presents the state of the art and a guide to help the choice of appropriated tools to assess patient cognition in studies on oncology and neurobehavior in animal models. In addition, current cognitive rehabilitation programs currently under evaluation are also discussed.

Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases.

Unlabelled: Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of α-emitting radionuclides, Tb, At, Pb, Bi and Ac; β-emitting radionuclides, Y, Tb and Lu; and Auger electron (AE)-emitters Ga, Zr, In and I, for targeted radionuclide therapy (TRT).

Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke.

In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia.

FMISO-PET-derived brain oxygen tension maps: application to glioblastoma and less aggressive gliomas.

Quantitative imaging modalities for the analysis of hypoxia in brain tumors are lacking. The objective of this study was to generate absolute maps of tissue pO from [F]-FMISO images in glioblastoma and less aggressive glioma patients in order to quantitatively assess tumor hypoxia. An ancillary objective was to compare estimated pO values to other biomarkers: perfusion weighted imaging (PWI) and tumor metabolism obtained from H-MR mono-voxel spectroscopy (MRS).

Assessment of behavioural deficits following ischaemic stroke in the marmoset.

Stroke is a common and devastating disease worldwide. Over the last two decades, many therapeutic approaches to ameliorate ischaemic stroke have been promising in animal studies but failed when transferred to the clinical situation. One of the possible explanations for these failures is the widespread use of animal models of cerebral ischemia that do not mimic the pathology encountered in the clinic.

Two-kidney one-clip is a pertinent approach to integrate arterial hypertension in animal models of stroke: Serial magnetic resonance imaging studies of brain lesions before and during cerebral ischemia.

Although chronic arterial hypertension (CAH) represents the major comorbid factor in stroke, it is rarely integrated in preclinical studies of stroke. The majority of those investigations employ spontaneously hypertensive rats (SHR) which display a susceptibility to ischemic damage independent of hypertension. Here, we used a renovascular model of hypertension (RH) to examine, with magnetic resonance imaging (MRI), brain alterations during the development of hypertension and after brain ischemia.

Imaging of brain oxygenation with magnetic resonance imaging: A validation with positron emission tomography in the healthy and tumoural brain.

The partial pressure in oxygen remains challenging to map in the brain. Two main strategies exist to obtain surrogate measures of tissue oxygenation: the tissue saturation studied by magnetic resonance imaging (SO-MRI) and the identification of hypoxia by a positron emission tomography (PET) biomarker with 3-[F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([F]-FMISO) as the leading radiopharmaceutical. Nonetheless, a formal validation of SO-MRI against FMISO-PET has not been performed.

Carbogen-induced increases in tumor oxygenation depend on the vascular status of the tumor: A multiparametric MRI study in two rat glioblastoma models.

The alleviation of hypoxia in glioblastoma with carbogen to improve treatment has met with limited success. Our hypothesis is that the eventual benefits of carbogen depend on the capacity for vasodilation. We examined, with MRI, changes in fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent signals in response to carbogen.

Imaging Modalities to Assess Oxygen Status in Glioblastoma.

Hypoxia, the result of an inadequacy between a disorganized and functionally impaired vasculature and the metabolic demand of tumor cells, is a feature of glioblastoma. Hypoxia promotes the aggressiveness of these tumors and, equally, negatively correlates with a decrease in outcome. Tools to characterize oxygen status are essential for the therapeutic management of patients with glioblastoma (i) to refine prognosis, (ii) to adapt the treatment regimen, and (iii) to assess the therapeutic efficacy.

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

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.

In Vivo Evaluation of Radiofluorinated Caspase-3/7 Inhibitors as Radiotracers for Apoptosis Imaging and Comparison with [18F]ML-10 in a Stroke Model in the Rat.

Purpose: The first biological evaluation of two potent fluorine-18 radiolabelled inhibitors of caspase-3/7 was achieved in a cerebral stroke rat model to visualize apoptosis.

Procedures: In vivo characteristics of isatins [(18)F]-2 and [(18)F]-3 were studied and compared by μPET to previously described 1-[4-(2-[(18)F]fluoroethyl)benzyl]-5-(2-methoxymethylpyrrolidin-1-ylsulfonyl)isatin ([(18)F]-1) and to 2-(5-[(18)F]fluoropentyl)-2-methyl-malonic acid ([(18)F]ML-10) used as a reference radiotracer in a rat stroke model.

Results: [(18)F]-2 and [(18)F]-3 were radiolabelled with high radiochemical purity and high specific radioactivity.

Molecular mechanisms of skeletal muscle atrophy in a mouse model of cerebral ischemia.

Background And Purpose: Loss of muscle mass and function is a severe complication in patients with stroke that contributes to promoting physical inactivity and disability. The deleterious consequences of skeletal muscle mass loss underline the necessity to identity the molecular mechanisms involved in skeletal muscle atrophy after cerebral ischemia.

Methods: Transient focal cerebral ischemia (60 minutes) was induced by occlusion of the right middle cerebral artery in C57BL/6J male mice.

Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat.

Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects.

Biochemical characterization of a Caspase-3 far-red fluorescent probe for non-invasive optical imaging of neuronal apoptosis.

Apoptosis is a regulated process, leading to cell death, which is involved in several pathologies including neurodegenerative diseases and stroke. Caspase-3 is a key enzyme of the apoptotic pathway and is considered as a major target for the treatment of abnormal cell death. Sensitive and non-invasive methods to monitor caspase-3 activity in cells and in the brain of living animals are needed to test the efficiency of novel therapeutic strategies.

Lack of secondary pathology in the thalamus after focal cerebral ischemia in nonhuman primates.

Remote regions such as the thalamus undergo secondary degeneration after cerebral ischemia. In rodents, the pathology in the thalamus is characterized by a robust inflammatory reaction, β-amyloid (Aβ) accumulation and calcification. Here we studied whether nonhuman primates subjected to middle cerebral artery occlusion (MCAO) display a similar pathology.

Brain ischemic injury in rodents: the protective effect of EPO.

Animal models constitute an indispensable tool to investigate human pathology. Here we describe the procedure to induce permanent and transient cerebral ischemia in the mouse and the rat. The model of transient occlusion of the middle cerebral artery (MCA) is performed by the insertion of an occlusive filament until the origin of the MCA while the permanent occlusion described in the mice is performed by a distal electrocoagulation of the MCA.

Angiopoietin-2 is vasoprotective in the acute phase of cerebral ischemia.

Most forms of cerebral ischemia are characterized by damage to the entire neurovascular unit, which leads to an increase in the permeability of the blood-brain barrier (BBB). In response to permanent focal cerebral ischemia in mice, we detected an early concomitant increase in the expression of the vascular endothelial growth factor (VEGF), a key inducer of vascular leakage and pathological blood vessel growth, and of angiopoietin-2 (Ang2), which is closely associated with VEGF in vascular remodeling. Thus, the aim of this study was to evaluate the role of Ang2 alone, or in combination with VEGF, in the acute phase of cerebral ischemia.

Maternal hypertension during pregnancy modifies the response of the immature brain to hypoxia-ischemia: sequential MRI and behavioral investigations.

Hypoxic-ischemic (HI) brain injury occurring during the perinatal period is still a major cause of mortality and morbidity. We assessed the impact of maternal hypertension, the most common medical disorder of pregnancy, on the anatomical and functional consequences of HI insult in the immature brain. Rat pups from spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto - WKY) dams were subjected to HI brain damage at post-natal day 7 (P7).