Optogenetically stimulating intact rat corticospinal tract post-stroke restores motor control through regionalized functional circuit formation.

Current neuromodulatory strategies to enhance motor recovery after stroke often target large brain areas non-specifically and without sufficient understanding of their interaction with internal repair mechanisms. Here we developed a novel therapeutic approach by specifically activating corticospinal circuitry using optogenetics after large strokes in rats. Similar to a neuronal growth-promoting immunotherapy, optogenetic stimulation together with intense, scheduled rehabilitation leads to the restoration of lost movement patterns rather than induced compensatory actions, as revealed by a computer vision-based automatic behavior analysis. Optogenetically activated corticospinal neurons promote axonal sprouting from the intact to the denervated cervical hemi-cord. Conversely, optogenetically silencing subsets of corticospinal neurons in recovered animals, results in mistargeting of the restored grasping function, thus identifying the reestablishment of specific and anatomically localized cortical microcircuits. These results provide a conceptual framework to improve established clinical techniques such as transcranial magnetic or transcranial direct current stimulation in stroke patients.

Optimization of the Surgical Approach in AVMs Using MRI and 4D DSA Fusion Technique : A technical note.

PURPOSE: Previously published data demonstrated the possibility of displaying the angioarchitecture of intracranial vascular malformations using time-resolved 3D imaging (4D digital subtraction angiography [DSA]). The purpose of our study was to prove the technical feasibility of creating fused images of time-resolved 3D reconstructions and MPRAGE MRI data sets and to check the reliability of the correct anatomical display of the angioma nidus and the venous drainage in the fused images of patients with intracranial arteriovenous malformations (AVM). PATIENTS AND METHODS: In this study 20 patients with intracranial AVM underwent pretherapeutic DSA and time-resolved 3D DSA in addition to MRI including MPRAGE sequences. The images were post-processed with the fusion software tool on a dedicated research workstation. The fusion of both imaging modalities was done semi-automatically with automatic co-registration software followed by a manual co-registration. RESULTS: Co-registered DSA/MRI data sets of 20 untreated AVMs were evaluated independently by two reviewers. Image fusion was successful in all 20 cases with an acceptable additional set-up time. The fused images were highly scored by the two raters in respect to their congruency of the dedicated regions. Precise anatomical localization of the nidus, the feeding arteries and the draining veins were possible with the merged images. CONCLUSION: Creating fused images of time-resolved 3D DSA and contrast-enhanced T1-weighted MPRAGE MR images might be beneficial for the preoperative and intrasurgical workflow in patients with AVMs. This new software tool fulfils the required quality and accuracy of the merged images. The clinical validation has to be proven in further studies.

Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke.

The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function.