Neural Plasticity Following Ischemia

Neural plasticity refers to the ability of one’s brain to change its structure and/or function in response to changes in behavior, environment, and neural processes. When a person suffers an ischemic brain injury, it often leads to hemisyndrome with motor and sensory deficits in the arm, leg, and face of one side. This article discusses the various ways that the existing network can be restructured and neuronal connections can be remodeled after the injury to enable partial or complete recovery of motor function. Spontaneous functional recovery after stroke develops through the overlapping sequence of events including a phase of axonal growth, spine remodeling and spine activation, and a phase of establishing and consolidating new neuronal networks. Shira Brickman graduated with a B.S. in Biology on May 2014 and will be attending SUNY Downstate's Physician Assistant Program. 24 rons. Dendritic spines are very plastic because they can change in shape, volume, and number in a small amount of time. These rapid changes in spine morphology that come as a result of the stroke could potentially influence electrical conduction of postsynaptic potentials (Brown CE, et. al., 2008). In order to study the rapid, ischemia induced changes in apical dendritic spines, researchers used the photothrombotic method, to induce a stroke in 20 adult male mice, in the part of the sensorimotor cortex that affects the forelimbs. Photothrombosis uses photo activation of injected light sensitive dye. Once it is illuminated, the dye is activated, and it produces singlet oxygen, an electronically excited state of molecular oxygen that causes platelet aggregation and thrombi formation to interrupt local blood flow. This method is used because it produces highly localized and reproducible lesions Results show that focal stroke triggers rapid spine loss and elongation of remaining spines in the peri-infarct cortex (Brown CE, et. al., 2008). The mouse brain was processed using Golgi-Cox staining. This is a silver staining that is used to view nerve tissues under light microscopy. This method only stains a limited number of entire cells at random, which allows neuroanatomists to track connections between neurons and to make the complex networking structure of many parts of the brain visible. They used this method to view the dendritic spine structures in the cortex at 2, 6 and 24 hours after the stroke. They selected pyramidal neurons from the peri-infarct primary motor cortex/M1and more distant secondary motor cortex/M2 to analyze the spine length and density. Two hours after the stroke, the loss of staining in the infarct core was already evident, while there was still relatively full labeling of neurons in the peri-infarct cortex. At the infarct border, the neurons had an asymmetric appearance because of the fully labeled dendrites on the non-ischemic side of the soma and fragmented dendrites on the other side projecting toward the infarct core. The researchers also measured the spine length of thousands of spines along the primary apical dendrites of neurons in the peri-infarct primary motor, secondary motor, and contralateral barrel cortex (layer 4 of somatosensory cortex). Analysis of this data revealed that spine length varied significantly from the control as a function of time after stroke and distance from the site of infarction. Spines were longer in the peri-infarct M1 but not in the other 2 regions. Additionally, within 24 hours after stroke, spine density levels dropped significantly in the peri -infarct M1. These findings suggest that during the first 24 hours after focal stroke, there is a loss of spines in the periinfarct cortex. However, the measurements of the spines that remained were longer than that of the controls (Brown CE, et. al., 2008). The data also suggests that the effects of ischemia are limited mainly to neurons close to the infarct border because we do not see significant changes in spine density in the more distant M2 and contralateral barrel cortex. Changes in dendritic spine length or shape can significantly alter the functional properties of neurons by helping to make new connections. What mechanisms are responsible for enhanced dendritic spine plasticity after stroke? Stroke induces certain gene expressions in the peri-infarct cortex that can regulate neuronal factors including GAP-43. GAP-43 is a growth or plasticity protein that is expressed at high levels during development of neurons in babies. However, the presence of GAP-43 levels in adult presynaptic membranes suggests that it continues to play a role in the functioning of certain synapses throughout life (Stroemer RP, et. al.,1995). Dendrites and Vasculature In addition to the plasticity of dendritic spines, the spontaneous recovery of functions after stroke is thought to be brought about through the reorganization and rewiring of surviving brain circuits. The surviving areas of the brain adjacent to the site of stroke reorganize and adopt new roles to compensate for the damage (Brown CE, et. al.,2007). Since dendritic spine turnover is the cause of rewiring during normal development and plasticity, it is likely to take part in bringing about changes that take place during and after stroke. By using in vivo two-photon imaging, researchers examine changes in dendritic and vascular structure in cortical regions recovering from stroke. In adult control mice, dendritic arbors were relatively stable, however after Shira Brickman 25 stroke, the organization of the dendrites in the peri-infarct cortex was altered. Using two-photon microscopy to monitor real time changes in dendritic structure, results indicate that cerebral infarction causes major changes in the peri-infarct dendrites and vasculature. For the experiment, adult male mice expressing yellow fluorescent protein were used in order to label/ highlight the specific neurons in layer 5 of the cortex. Once again, the photothrombotic method was used to induce the infarction to the cortical representation of the forelimb. In order to study the organization of the dendrites, the apical dendritic tufts of the highlighted neurons were imaged with two photon imaging every hour for a 6 or 7 hour period. In control mice, the apical dendritic tufts and vasculature were intertwined with one another without any particular spatial relationship. However, these components in the peri-infarct cortex of injured mice displayed a very different pattern of organization; the dendrites and vasculature appear to be parallel with one another and radiate outward from the edge of the infarct border. In addition, researchers took note of the blood flow velocity of the plasma moving through the lumen of the capillaries. While they found that blood flow velocity was similar to that of the control, they observed that the density of the blood vessels in the periinfarct region increased over time (Brown CE, et. al.,2007). Given the importance of dendrites in neurotransmission, these changes in dendrite structure may very possibly aid in the functional and/or behavioral changes in post stroke victims.