Abstract TP238: Optogenetic Stimulation Of Cortico-thalamic Circuits Promotes Oligodendrogenesis In The Degenerative Thalamus After Stroke

Introduction: Loss of neuronal activity after stroke can impact many activity-dependent processes including oligodendrocyte maturation and myelination. The cortico-thalamic circuit is particularly disrupted after cortical stroke, resulting in secondary axonal degeneration in the thalamus. This secondary thalamic injury is associated with worsened functional outcomes. Increasing neuronal activity by optogenetic stimulation promotes oligodendrogenesis and myelination in normal conditions. In this study, we use optogenetic stimulation to selectively re-activate the cortico-thalamic circuit after stroke and examine its effects on oligodendrocytes in the degenerative thalamus. Methods: C57BL6 male mice (6-8 weeks old) were injected AAV1-CaMKIIa-hChR2 virus in the ipsilesional somatosensory cortex and implanted an optic fiber in the ipsilesional thalamus. After six weeks, the left middle cerebral artery was permanently occluded to generate infarct in iS1. Stimulated mice were given daily optogenetic stimulations between Post-stroke Day (PD) 4 to 14. Brain sections were immunostained to detect primary cortical injury and secondary thalamic injury (NeuN), and neuroinflammation (CD68) and oligodendrogenesis (Olig2 and CC1) in the thalamus. Results: ChR2 is specifically expressed in the somatosensory cortico-thalamic tract. Neuronal loss and robust neuroinflammation were observed in iTH after stroke, but there was no significant difference between non-stimulated and stimulated mice. However, stimulated mice exhibited 5.5 times increase in the numbers of mature oligodendrocytes (Olig2 + CC1 + , p=0.02, n=5/group), and 5.4 times increase in the numbers of oligodendrocyte progenitor cells (Olig2 + , p=0.03) in the degenerative thalamus. Conclusion: Our data demonstrate that selective re-activation of the cortical-thalamic circuits promoted oligodendrogenesis in the secondary degenerative thalamus after stroke. As the secondary thalamic injury allows an extended treatment window, targeting secondary injury is a promising approach to improve stroke recovery. Current studies are testing the effects of cortico-thalamic circuit stimulation in myelination in the degenerative thalamus and functional outcome after stroke.