Increases in the T1 of brain tissue, which give rise to dark or hypointense areas on T1-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 T1 increases remains unclear. Using a multiparametric MRI approach and well-defined experimental models, we have experimentally induced increases in tissue T1 to determine the underlying cellular basis of such changes. We have shown that a rapid acute increase in T1 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 T1 relaxation and changes in other MRI parameters (apparent diffusion coefficient, T2 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 T1 signal change induced by intrastriatal ET-1 injection. These findings suggest that an increase in T1 relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion. Early changes in T1 may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS.
Suppression of α-synuclein propagation after intrastriatal injection in FABP3 null mice
