MR Imaging and Spectroscopy of Brain Plasticity after Experimental Stroke

Abstract

Ischemic stroke is a major cause of death and long-term disability in the Western society. It leaves more than half of the patients dependent on daily assistance and is considered to be a substantial social burden. Still, most patients exhibit a certain degree of spontaneous functional recovery in the the following weeks or months after stroke. Functional recovery is thought to be related to brain plasticity, which refers to the capability of the brain to compensate for loss of function through reorganization of neural networks. The prolonged time-course of brain plasticity in relation to spontaneous functional recovery may hold great potential for long-term therapeutic interventions that are aimed at facilitating plastic adaptation. Knowledge about the mechanisms responsible for functional recovery may aid in the development of new rehabilitation strategies directed at the improvement of functional outcome. The studies in this thesis are devoted to unravelling the complex pattern of neural reorganization after stroke in rats, using multi-parametric in vivo MR methods. Studies were aimed at the detection of long-term functional and/or structural alterations in perilesional and remote areas that contribute to post-stroke loss and recovery of function. Special focus was given to the potential of advanced MRI and MRS techniques to study post-stroke reorganization, which can be measured over time and correlated with functional recovery. Changes in tissue morphology, neuroanatomy and metabolic function in (sub)acute and chronic stages that may ultimately compensate for lost function after stroke are described, and can be categorized in three distinct stages. At the acute stage, critically impaired sensorimotor function is accompanied by edema formation, reduced energy metabolism and neurotransmission, and disturbed neuronal connectivity. In the following period, early ischemia-induced structural and functional damage recovers in conjunction with restoration of sensorimotor function. Then, at chronic stages after stroke, when functional recovery has reached a plateau stage, there is a further enhancement in neuroanatomical connectivity. The studies in this thesis contribute to an improved knowledge about the neural mechanisms that may underlie post-stroke loss and recovery of function. We have demonstrated evolving neuroanatomical and metabolic remodeling after stroke using multiparametric MR techniques. The spatio-temporal profile of neuronal remodeling suggests that perilesional and connected areas play a key role in neuroplasticity and recovery of function, which continues for months following stroke. This may open up possibilities for long-term treatment of stroke patients directed at the improvement of functional outcome.