Normalization of T2 relaxation time and apparent diffusion coefficient in relation to the inflammatory changes in the substantia nigra of rats with focal cerebral ischemia

Abstract

Background

Focal cerebral ischemia results in delayed neurodegeneration in remote brain regions, such as the substantia nigra. To date, a reasonable explanation is still lacking regarding the correlation of magnetic resonance (MR) signal pseudo-normalization following a transient abnormal change and subsequent progressive pathological damage.

Purpose

To characterize the substantia nigra following middle cerebral artery occlusion and to evaluate the potential pathophysiological changes associated with the pseudo-normalization of MR signals in the substantia nigra at the subacute stage after stroke onset.

Material and Methods

Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion. During the occlusion of single middle cerebral artery, computed tomography (CT) perfusion was acquired to observe the blood flow perfusion in the primary ischemic striatum and ipsilateral substantia nigra. Next, the MR T2 relaxation time and apparent diffusion coefficient changes within the substantia nigra were determined on days 1, 3, 7, and 14 after stroke onset, and compared with immunohistochemistry for microglia activation and astrogliosis.

Results

Twenty-four rats with strong hypoperfusion in the primary ischemic territory and no alterations of the perfusion in the ipsilateral substantia nigra detected both visually and measurably during the middle cerebral artery occlusion were further studied. All animals showed MR pseudo-normalization with T2 relaxation time and apparent diffusion coefficient recovered in the ipsilateral substantia nigra at the subacute phase following focal cerebral ischemia. Normalization of the MR signals corresponded well with the spatio-temporal occurrence of microglia activation and astrogliosis.

Conclusion

The pseudo-normalization of T2 relaxation time and apparent diffusion coefficient reflects the neuroinflammatory changes that accompany activation of microglia and astrocytes in the ipsilateral substantia nigra following middle cerebral artery occlusion.