RESUMO
Following a stroke, an inflammatory response occurs, characterized by an increased blood-brain barrier permeability, expression of endothelial trafficking molecules, and infiltration of immune cells. Adhesion molecules expressed on activated brain endothelial cells are potential biomarkers of intraparenchymal inflammation. However, in current clinical practice, it is not possible to measure endothelial activation using clinically available imaging. Using targeted micro-sized particles of iron oxide (MPIO), immuno-MRI enables the detection of endothelial adhesion molecules at high resolution and, consequently, facilitates the detection of stroke-induced brain inflammation. In this review, we highlight the most recent studies that used immuno-MRI in models of neurovascular disorders, including transient ischemic attack, ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage. We also discuss the potential of immuno-MRI in clinical practice and the necessary next steps for its implementation in patients.
RESUMO
Tissue-type plasminogen activator (tPA) is a protease known for its fibrinolytic action but is also involved in physiological and pathophysiological aging processes; including amyloid elimination and synaptic plasticity. The aim of the study was to investigate the role of tPA in cognitive and brain aging. Therefore, we assessed the links between tPA plasma concentration and cognition, structural MRI, FDG-PET and Flobetapir-PET neuroimaging in 155 cognitively unimpaired adults (CUA, aged 20-85 years old) and 32 patients with Alzheimer's disease (ALZ). A positive correlation was found between tPA and age in CUA (p < 0.001), with males showing higher tPA than females (p = 0.05). No significant difference was found between ALZ patients and cognitively unimpaired elders (CUE). Plasma tPA in CUA negatively correlated with global brain volume. No correlation was found with brain FDG metabolism or amyloid deposition. Age-related tPA changes were associated to changes in blood pressure, glycemia and body mass index. Within the ALZ patients, tPA didn't correlate with any cognitive or neuroimaging measures, but only with physiological measures. Altogether our study suggests that increased tPA plasma concentration with age is related to neuronal alterations and cardiovascular risk factors.
RESUMO
PURPOSE: The objective of the present review is to provide an overview of the available clinical and preclinical data supporting the existence of an "inflammatory penumbra" in ischemic stroke. FINDINGS: Recent data from clinical trials suggest the existence of an inflammatory area at risk, surrounding the initial ischemic lesion and secondarily infiltrated by lymphocytes, that is ultimately recruited by the ischemic core: called the "inflammatory penumbra." Experimental results support this concept. Lymphocytes, especially T-cells, enter the brain in the perilesional area in a vascular-cell adhesion molecule-1 dependent manner and participate in delayed neuronal cell death. METHODS: For writing this review, we used the more recent publications in the field, including the preclinical and clinical studies. We have also used our own experise in the field of in vivo imaging of inflammatory processes. DISCUSSION: Consequently, the intensity of the inflammatory reaction and the size of the inflammatory penumbra may vary considerably in patients, as it is the case in experimental stroke models in mice. By analogy with the ischemic penumbra of the acute phase of stroke, this secondary inflammatory penumbra represents a therapeutic opportunity during the subacute phase of stroke. Large clinical trials that target lymphocyte trafficking are currently taking place. However, to improve the benefit of such therapeutic strategies, adequate patient selection may be mandatory. CONCLUSION: In this context, innovative imaging methods including magnetic resonance imaging of adhesion molecules may contribute to noninvasively detect this inflammatory penumbra and thus to select patients eligible for such therapy.