Material and mechanical factors： new strategy in cellular neurogenesis

Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma- cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material （chemical patterning, micro/nano-topography, carbon nanotube, graphene） and mechanical （static cue from substrate stiffness, dynamic cue from stretch and flow shear） stimulations of cellular neuro- genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.     

The arterial wall response to intimal injury in an experimental model

Repair of occult arterial injuries is advocated to prevent thrombosis, arteriovenous fistula, and pseudoaneurysm formation. However, recent clinical series describe the healing of arterial intimal injuries and recommend nonoperative therapy. To investigate the arterial wall response to intimal injury, we created intimal flaps in 46 canine femoral arteries. The intimal flaps were imaged by arteriography, angioscopy, and intravascular ultrasound acutely, and at one and three weeks and five months post-injury. Lumen area was measured using caliper techniques (arteriography) and computerized video planimetry (angioscopy, intravascular ultrasound). Intimal and medial thickness were measured by intravascular ultrasound prior to harvest for histologic evaluation by light microscopy. Analysis of 32 patent arteries was performed after exclusion of 14 thrombosed arteries. Residual lumen area (mm²) correlated closely among the imaging modalities at one week (8.7±1.1, 7.3±2.0, 6.9±1.8), three weeks (4.2±0.9, 2.9±1.0, 2.7±0.8), and five months (5.3±0.9, 5.0±0.5, 5.0±0.9). Maximal intimal and medial thickness occurred three weeks post-injury, coincident with the maximal reduction in lumen area. Although intimal injuries can cause acute and delayed arterial thromboses, observation may be appropriate in selected cases. The evaluation of those patients chosen for nonoperative therapy should extend beyond three weeks, as this is the time of maximal arterial wall response with a continued potential for adverse clinical events.Presented at the 16th Annual Meeting of the Peripheral Vascular Surgery Society, June 2, 1991, Boston, Massachusetts.     

Thrombin binding to platelets and their activation in plasma

Summary. The interactions of α-thrombin with platelets are critical in haemostasis and arterial thrombosis. This study established methods for characterizing the binding of α-thrombin to platelets and some of its consequences in platelet-rich plasma. The binding of α-thrombin to platelets and the subsequent platelet activation were quantified by flow cytometry, using affinity purified polyclonal antibodies to human α-thrombin and a monoclonal antibody to GMP-140, respectively. Dose-dependent binding of α-thrombin to platelets and their activation occurred in parallel, both reaching the maxima for each enzyme concentration within 10 s after → 1.0 n m α-thrombin was added to recalcified PRP containing 1 μ m recombinant tick anticoagulant peptide. The tick anticoagulant peptide abrogated prothrombin activation in the platelet-rich plasma. α-Thrombin binding to platelets, and their activation, were abrogated by a monoclonal antibody to the hirudin tail-like domain of the seven transmembrane thrombin receptor on platelets. Therefore this receptor represents an important site for α-thrombin binding to platelets suspended in plasma. d -Phe-Pro-ArgCH₂-α-thrombin only bound to platelets when its concentration was → 100 n m , and it did so without inhibiting platelet activation by α-thrombin. Whereas concentrations of hirudin equimolar to those of α-thrombin failed to abrogate α-thrombin-mediated activation of platelets, a 10-fold molar excesses of hirudin over α-thrombin abrogated α-thrombin binding to platelets. The demonstration that → 1.0 n m α-thrombin can bind to platelets and initiate their activation raises the possibility that the levels of thrombin generated in venous and arterial thrombosis contribute to platelet activation in vivo .