Abstract WP100: Investigation of Secondary Thalamic Injury After Ischemic Stroke: A Time Course Study

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Introduction: After a cortical stroke, secondary degeneration can occur in remotely connected regions such as thalamus. This progressive secondary thalamic injury leads to somatosensory dysfunctions and hinders recovery. The pathophysiology of primary ischemic injury has been well characterized; however, the mechanism underlying secondary thalamic injury is poorly understood. We conducted a time course study to identify the critical time window of thalamic injury development after stroke and to investigate the involved mediators. Methods: Cortical ischemic stroke was generated by permanent occlusion of left middle cerebral artery in male C57BL6J mice (12-15 weeks). Brain sections were collected on post-stroke days (PD) 1, 3, 7, 14 and 28. Fluoro Jade C and TUNEL staining were used to detect degenerative injury and apoptosis, respectively. Immunostaining were used to detect neuronal loss (NeuN & MAP2) and inflammatory responses (CD68 & GFAP). Results: In the somatosensory cortex, degenerative injury and apoptosis were detected as early as PD1. Reduced NeuN and MAP2 expression confirmed the cortical neuronal injury starting at PD1. Activated microglia (CD68) were initially detected around the infarct at PD1 and gradually showed in the infarct core at PD14. Activated astrocytes (GFAP) appeared sparsely around the infarct on PD3 and became densely packed and elongated at PD7. In the ipsilesional thalamus, degenerative injury and apoptosis were detected at PD7 and became aggravated on day 28, indicating a development of thalamic injury. Reduced NeuN and MAP2 expression in the thalamus began at PD14. Activated microglia were detected at PD1 and activated astrocytes were detected at PD3 in the ipsilesional thalamus. Clustered microglia/astrocytes started at PD7 and became more densely at PD14 and 28. Conclusion: Our data shows that thalamic degenerative injury begins on PD7 and continues to develop until at least PD28. Our data also shows robust inflammatory responses during thalamic injury development. Future study will identify the subtypes of activated microglia/astrocyte and the related molecular mediators. Our findings will enrich the understanding of thalamic injury and define specific cellular and molecular targets for stroke treatments.