Search

During the neonatal period, activity-dependent neural-circuit remodelling coincides with growth and refinement of the cerebral microvasculature (1,2). Whether neural activity also influences the patterning of the vascular bed is not [...]

Cerebral microvascular occlusion is a common phenomenon throughout life (1,2) that might require greater recognition as a mechanism of brain pathology. Failure to recanalize microvessels promptly may lead to the disruption of brain circuits and significant functional deficits (3). Hemodynamic forces and the fibrinolytic system (4) are considered to be the principal mechanisms responsible for recanalization of occluded cerebral capillaries and terminal arterioles. Here we identify a previously unrecognized cellular mechanism that may also be critical for this recanalization. By using high-resolution fixed-tissue microscopy and two-photon imaging in living mice we observed that a large fraction of microemboli infused through the internal carotid artery failed to be lysed or washed out within 48 h. Instead, emboli were found to translocate outside the vessel lumen within 2-7 days, leading to complete re-establishment of blood flow and sparing of the vessel. Recanalization occurred by a previously unknown mechanism of microvascular plasticity involving the rapid envelopment of emboli by endothelial membrane projections that subsequently form a new vessel wall. This was followed by the formation of an endothelial opening through which emboli translocated into the perivascular parenchyma. The rate of embolus extravasation was significantly decreased by pharmacological inhibition of matrix metalloproteinase 2/9 activity. In aged mice, extravasation was markedly delayed, resulting in persistent tissue hypoxia, synaptic damage and cell death. Alterations in the efficiency of the protective mechanism that we have identified may have important implications in microvascular pathology, stroke recovery and age-related cognitive decline., Cerebral function and viability are dependent on uninterrupted blood flow through the microvasculature for the adequate delivery of oxygen and glucose (5). Thus, robust mechanisms must have evolved to ensure [...]

Author(s): Jaime Grutzendler; Narayanan Kasthuri; Wen-Biao Gan (corresponding author) The structural dynamics of synapses probably has a crucial role in the development and plasticity of the nervous system. In the [...]