Mapping the Stroke “RE-Connectome”

Mark Goldberg, MD

Professor of Neurology

Associate Vice President for Strategic Research Initiatives

UT Health San Antonio

Friday, September 30, 2022

11 AM CST – 12 PM CST

Join from the webinar link

https://utsa.webex.com/utsa/j.php?MTID=m732b1ddde75e79c34bcb0177fe4e1d57

How can the brain restore its function when parts are irreversibly injured?  Stroke, or “brain attack” occurs when an artery supplying one part of the brain becomes blocked by atherosclerosis or blood clot.  The blockage may resolve spontaneously, or hospital stroke specialists may use drugs or catheters to remove the clot.  But if the artery remains blocked for several hours the tissue will be permanently damaged, and the stroke patient will have deficits that reflect the brain region, such as loss of strength, sensation, vision, speech or memory.   Surprisingly, most stroke patients have at least partial recovery of function over the next 90 days, even though the injured neurons and other brain cells do not regenerate.  This occurs because of neural plasticity, the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its structure, functions, or connections.

Our lab studies a unique form of post-stroke plasticity in a mouse model.   After a targeted injury of the primary motor cortex on one hemisphere, the axons from cortex to spinal cord (corticospinal tract) degenerate and muscle function is impaired.   Within 2-4 weeks, axons from the opposite – uninjured –  corticospinal tract send new collateral sprouts across the spinal cord, where they form synapses that replace the ones lost after stroke.  This is a remarkable form of plasticity because the neurons responsible for repair are far from the location of injury.  Neurons and supporting glial cells activate molecular programs of axon growth that do not normally occur in the adult nervous system.

We’ve developed a microscopy and image analysis pipeline to generate large scale 3D data of the full set of brain and spinal connections that change after injury (which we term the “RE-Connectome”).  Viral vectors and transgenic mice express fluorescent proteins in axons and presynaptic terminals.   Mouse brains and spinal cords are removed and fixed after stroke and imaged using a serial two-photon tomography microscope.  The pipeline for whole brain image analysis includes supervised machine learning (pixel-wise random forest models via the “ilastik” software package) followed by registration to a standardized 3-D atlas of the adult mouse brain or spinal cord.  In this talk, we’ll present some conclusions from our reconnectome data, and review challenges with image segmentation.   This model of nervous system plasticity may provide approaches to promoting resilience in human stroke or in neuromorphic networks.