Temporal Profiles of Axon Terminals, Synapses and Spines in the Ischemic Penumbra of the Cerebral Cortex

Abstract

Background and Purpose-Because the recovery process of axon terminals, synapses, and spine-dendrites in the ischemic penumbra of the cerebral cortex is obscure, we studied the temporal profile of these structures up to 12 weeks after the ischemic insult, using a gerbil model. Methods-Stroke-positive animals were selected according to their stroke index score during the first 10-minute left carotid occlusion done twice with 5-hour interval. The animals were euthanized at various times after the second ischemic insult. Ultra-thin sections including the 2nd to 4th cortical layers were obtained from the neocortex coronally sectioned at the infundibular level, in which the penumbra appeared. We counted the number of synapses, spines and multiple synapse boutons, measured neurite thickness, and determined the percent volume of the axon terminals and spines by Weibel point counting method. Results-The number of synapses, synaptic vesicles and spines and the total percent volume of the axon terminals and spines decreased until the 4th day. From 1 to 12 weeks after the ischemic insult, these values increased to or exceeded the control ones, and neuritic thickening and increase in number of multiple synapse boutons occurred. Conclusions-In the ischemic penumbra, the above structures degenerated, with a reduction in their number and size, until 4 days and then recovered from 1 to 12 weeks after the ischemic insult.

Extensive Turnover of Dendritic Spines and Vascular Remodeling in Cortical Tissues Recovering from Stroke

“…Although it is conceivable that the time course or magnitude of changes in spine turnover may differ depending on the model of stroke, we doubt that the direction of stroke-induced changes in turnover (i.e., increased spine formation during recovery) would be different. Consistent with this idea, other groups using different models of stroke and histological assays have found that spine density drops initially after stroke and gradually recovers over time (Corbett et al, 2006;Ito et al, 2006). In addition, recent data from our laboratory has shown that the dendritic morphology of acutely ischemic layer 5 neurons in photothrombotic models is very similar to that observed in a middle cerebral artery occlusion model (Enright et al, 2007).…”

“…One mechanism through which this may occur is by rearranging existing dendritic arbors or by making new synaptic contacts. In accordance with this, postmortem investigations have reported that cortical injury significantly alters branch complexity, spine density, and synapse number in peri-infarct cortical dendrites (Gonzalez and Kolb, 2003;Ito et al, 2006). Histochemical markers of axonal sprouting and presynaptic terminals such as GAP-43 and synaptophysin, respectively, become progressively enriched in the peri-infarct cortex (Stroemer et al, 1995), suggesting that peri-infarct regions may be a prime site of synaptic reorganization after stroke.…”

Thalamic T-Type Ca2+Channels Mediate Frontal Lobe Dysfunctions Caused by a Hypoxia-Like Damage in the Prefrontal Cortex

“…S1, available at www.jneurosci.org as supplemental material). The damaged area detected in MR images was further characterized by hematoxylin/eosin staining, and we found that Co-wire implantation resulted in clear signs of hypoxic damage as measured by the increase of ghost cells (Ito et al, 2006) and inflammatory angiogenesis (Sharp and Bernaudin, 2004) visualized by blood vessels filled with red blood cells (RBCs) (Fig. 1b,c; supplemental Fig.…”

Degeneration of Astrocytic Processes and Their Mitochondria in Cerebral Cortical Regions Peripheral to the Cortical Infarction

“…Placing a 1.0ϫ1.0 cm quadratic lattice on 40.2Ϯ2.1 evenly distributed EM photographs (magnified 18 690 times) of neuropil (Supplemental Figure II) for 3 animals in each time group, we determined the percent-volume of the APs in the neuropil by using the point-counting method 12,15 (Supplemental Table II). By this method we counted the number of intersecting points of the lattice touched by the cut-ends of the APs among an average of 17 163.2Ϯ890.4 evenly distributed points in the neuropil of the EM pictures for 3 animals in each time group, and converted the counted number in each EM picture to the number among 100 intersecting points of the lattice of each EM picture (percent volume).…”

“…9,[11][12][13] In this model, by dividing the ischemic insult into 2 parts, the mortality rate of the animals attributable to epileptic seizure was decreased drastically; and the infarction size became uniform so that focal cerebral cortical infarction evolved only in the coronal face sectioned at the chiasmatic level (Face A), and only DSNN matured in the coronal face sectioned at the infundibular level (Face B; see Supplemental Figure I, available online at http://stroke.ahajournals.org).…”