Contractile apparatus in CNS capillary pericytes.

Significance: Whether or not capillary pericytes contribute to blood flow regulation in the brain and retina has long been debated. This was partly caused by failure of detecting the contractile protein α -smooth muscle actin ( α -SMA) in capillary pericytes. Aim: The aim of this review is to summarize recent developments in detecting α -SMA and contractility in capillary pericytes and the relevant literature on the biology of actin filaments. Results: Evidence suggests that for visualization of the small amounts of α -SMA in downstream mid-capillary pericytes, actin depolymerization must be prevented during tissue processing. Actin filaments turnover is mainly based on de/re-polymerization rather than transcription of the monomeric form, hence, small amounts of α -SMA mRNA may evade detection by transcriptomic studies. Similarly, transgenic mice expressing fluorescent reporters under the α -SMA promoter may yield low fluorescence due to limited transcriptional activity in mid-capillary pericytes. Recent studies show that pericytes including mid-capillary ones express several actin isoforms and myosin heavy chain type 11, the partner of α -SMA in mediating contraction. Emerging evidence also suggests that actin polymerization in pericytes may have a role in regulating the tone of downstream capillaries. Conclusions: With guidance of actin biology, innovative labeling and imaging techniques can reveal the molecular machinery of contraction in pericytes.

Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: A hyperacute role for neutrophils in persistent traffic jams.

Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in salvageable penumbra after reperfusion. These stalls, which are different from permanent cellular plugs of no-reflow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling slowly through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments under reperfused conditions. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. Decreased number and duration of stalls were associated with improvement in penumbral blood flow within 2-24 h after reperfusion along with increased capillary oxygenation, decreased cellular damage and improved functional outcome. Thereby, dynamic microcirculatory stall phenomenon can be a contributing factor to ongoing penumbral injury and is a potential hyperacute mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.

Neuro-ophthalmology of subacute sclerosing panencephalitis: two cases and a review of the literature.

PURPOSE OF REVIEW: To review the literature on early visual manifestations of subacute sclerosing panencephalitis (SSPE) with regard to two patients who had visual problems preceding the onset of neurological symptoms. One patient had cortical visual disturbances and the other had visual loss due to retinal pigment epithelial changes. RECENT FINDINGS: SSPE is a chronic encephalitis characterized by a history of measles infection and a progressive disease of the central nervous system that still occurs frequently in countries with insufficient measles immunization. Visual manifestations can occur as a result of involvement of the pathways that lead from the retina to the occipital cortex during the course of the disease, but are rare as a presenting sign. Fundus changes, especially macular retinitis and macular pigment disturbances, appear to be the most common ocular manifestations of SSPE. SUMMARY: Ophthalmologists must be aware that SSPE can knock their door with ocular findings of SSPE, months or years before the onset of neurological symptoms.