Tissue Microenvironments within Functional Cortical Subdivisions Adjacent to Focal Stroke

Abstract

Stroke produces a region of complete cell death and areas of partial damage, injury, and gliosis. The spatial relationship of these regions of damage to the infarct core and within spared neuronal circuits has not been identified. A model of cortical stroke was developed within functional subsets of the somatosensory cortex. Infarct size, regions of apoptosis, oxidative DNA damage, heat shock protein induction, and subtypes of reactive gliosis were precisely mapped with the somatosensory body map, quantified, and interrelated. Three tissue microenvironments were recognized: zones of partial ischemic damage, heat shock protein induction, and distributed gliosis. These three zones involved progressively more distant cortical regions, each larger than the infarct core. The zone of partial ischemic damage represents an overlap region of apoptotic cell death, oxidative DNA damage, loss of synaptic connections, and local reactive gliosis. The zone of distributed gliosis occupies distinct functional areas of the somatosensory cortex. The tissue reorganization induced by stroke is much larger than the stroke site itself. Adjacent tissue microenvironments are sites of distinct reactive cellular signaling and may serve as a link between the processes of acute cell death and delayed neuronal plasticity after focal stroke.

Stroke-Evoked Angiogenesis Results in a Transient Population of Microvessels

“…to distant zones of gliosis (Katsman et al, 2003). The present study confirms observations of microvessel hyperdensities in the ischemic infarction zone (Manoonkitiwongsa et al, 2001a) and is consistent with previous studies that indicate that angiogenesis induced by ischemia is not a widespread reaction of parenchymal microvessels in the entire ischemic zone distal to MCA occlusion (Marti et al, 2000;Zhang et al, 2000Zhang et al, , 2002.…”

A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke

“…Our Western blot and in situ hybridization data show that this ephrin-A5 forward signaling activates EphA in a surprisingly broad area of periinfarct cortex, extending from the stroke site into virtually the entire ipsilateral mouse cortical hemisphere. Although reactive astrocytes cluster tightly near the infarct core, they can be found in decreasing numbers throughout the ipsilateral cortical hemisphere (39). These data indicate that although the hemisphere ipsilateral to the stroke appears morphologically intact and structurally "normal," a distributed population of reactive astrocytes locks down cortical projection systems through ephrin-A5 blockade.…”

“…This time point for drug delivery was chosen because it falls within the time frames of poststroke ephrin-A5 up-regulation and axonal sprouting (4,5,14). In addition, at 7 d poststroke, the microenvironment of the infarct core has stabilized a boundary of reactive astrocytes around the stroke cavity and implantation of hydrogel can be made without damage to adjacent tissue (15). Twenty-one days after stroke, microinjection of the tracer biotinylated dextran amine (BDA) was made into forelimb sensorimotor cortex, and animals were killed at 28 d after stroke ( Fig.…”

Rodent models of focal stroke: Size, mechanism, and purpose

“…90,94 This is supported by the finding of oxidative damage within the infarct core, rather than progressively distributed in peri-infarct areas as in other models. 66,111,114,115 Also the simultaneous disruption of endothelial integrity and rapidly progressive infarction in a small cortical volume results in substantial local vasogenic edema.…”

“…One model takes advantage of the arterial branching pattern of the MCA in the parietal region 130 to focally interrupt blood supply to the somatosensory barrel cortex. 115,131 The cortical representation of each facial whisker forms a structural module, or barrel, that is easily visualized in the adult brain. Together, these modules constitute the barrel cortex, which forms a significant part of the entire rodent cortex (FIG.…”