Acute Astrocyte Activation in Brain Detected by Mri: New Insights into T₁ Hypointensity

Abstract

Increases in the T(1) of brain tissue, which give rise to dark or hypointense areas on T(1)-weighted images using magnetic resonance imaging (MRI), are common to a number of neuropathologies including multiple sclerosis (MS) and ischaemia. However, the biologic significance of T(1) increases remains unclear. Using a multiparametric MRI approach and well-defined experimental models, we have experimentally induced increases in tissue T(1) to determine the underlying cellular basis of such changes. We have shown that a rapid acute increase in T(1) relaxation in the brain occurs in experimental models of both low-flow ischaemia induced by intrastriatal injection of endothelin-1 (ET-1), and excitotoxicity induced by intrastriatal injection of N-methyl-D-aspartate (NMDA). However, there appears to be no consistent correlation between increases in T(1) relaxation and changes in other MRI parameters (apparent diffusion coefficient, T(2) relaxation, or magnetisation transfer ratio of tissue water). Immunohistochemically, one common morphologic feature shared by the ET-1 and NMDA models is acute astrocyte activation, which was detectable within 2 h of intracerebral ET-1 injection. Pretreatment with an inhibitor of astrocyte activation, arundic acid, significantly reduced the spatial extent of the T(1) signal change induced by intrastriatal ET-1 injection. These findings suggest that an increase in T(1) relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion. Early changes in T(1) may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS.

PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia

“…Our most pronounced effects were observed when treatment was started 3 hrs post-stroke, which is in line with astrocyte processes increasing within hours of brain injury 50 . Taken together these results imply that PEG-IGF-I may augment the protective activity of astrocytes for an acute period after insult and mitigate detrimental inflammatory and immunological processes in the lesion site, thus supporting functional recovery.…”

Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

“…In general, there are no specific markers of changes in either oligodendrocytes or astrocytes. Recent evidence suggests that hypointense white matter lesions on T1w imaging may indicate reactive astrocytes (Sibson et al, 2008). Increases in microglia often accompany inflammation, which can be detected using contrast agents, either gadolinium or superparamagnetic iron oxide (SPIO) particles.…”

Elusive roles for reactive astrocytes in neurodegenerative diseases

“…Increased T1 relaxation time is observed by magnetic resonance imaging (MRI) in acute models of ischemia and excitotoxicity. Arundic acid, an inhibitor of astrocyte reactivity, normalizes it, but the molecular basis for such changes in NMR signals is unclear (Sibson et al, 2008 ). NMR-spectroscopy (MRS) allows the quantification of abundant brain metabolites, including myo-inositol, glutamine and choline which are enriched in glial cells.…”