Overcoming the blood–brain barrier: the role of nanomaterials in treating neurological diseases

Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood–brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial‐based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease‐targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial‐mediated treatment of neurological diseases

A velocity profile equation for blood flow in small arterioles and venules of small mammals in vivo and an evaluation based on literature data

An empirical parametric equation with 2 bluntness parameters was introduced for describing the velocity profile of blood in the small arterioles and venules of small mammals, in vivo, with the basic approximations of the axisymmetric flow in cylindrical geometry, zero velocity at the wall and a blunter than parabolic flow profile. The purpose was to evaluate the usefulness of this equation in describing the velocity profile and in estimating the volume flow when only one velocity measurement is available near the vessel axis. The equation was tested on 17 velocity profiles (9 arteriolar and 8 venular) previously measured by particle image velocimetry (PIV) techniques, at diameters ranging from 17 to 38.6 mu m. The correlation coefficients of each experimental profile were higher than 0.96. The average relative error-bias measured at 10 radial segments ranged between -5% to 1%, leading to an average relative volume flow estimation error for all the 17 velocity profiles of -1.8% with a standard deviation of 4.3%

The importance of ophthalmic artery hemodynamics in patients with atheromatous carotid artery disease

Aim. The aim of this paper was to provide an insight on the role of the ophthalmic artery blood flow changes due to significant carotid stenosis and the effects of carotid revascularization on the eye and cerebral circulation. Methods. An electronic search (Medline) of the English literature was attempted. Measurements of Peak Systolic Velocity (PSV), end-diastolic velocity (EDV), mean velocity (Vmean), Resistance Index (RI) and flow direction, obtained in OA and its branches using transcranial Doppler, in to patients with significant stenosis >70% subjected to surgical or endovascular treatment, or in those with occlusion (unilateral or bilateral), symptomatic or not, in both eyes, prior to or/and after endarterectomy or stenting. Results. As the degree of internal carotid artery (ICA) stenosis increases, the PSV in ophthalmic artery (OA) decreases. In severe stenoses the flow is not detectable or a reversed flow may be present. Following carotid endarterctomy or stenting, in almost all patients antegrade flow was detected, while in the patients with preoperative antegrade flow, an increase of the velocities was detected postoperatively. Conclusion. The reduced blood flow in the OA has consequences in the eye circulation. OA contributes to the collateral pathways in the perfusion of the brain but the importance of this collateral pathway has not been completely clarified. [Int Angiol 2011;30:547-54

Blood velocity pulse quantification in the human conjunctival pre-capillary arterioles

Axial red blood cell velocity pulse was quantified throughout its period by high speed video microcinematography in the human eye. In 30 conjunctival precapillary arterioles (6 to 12 mu m in diameter) from 15 healthy humans, axial velocities ranged from 0.4 (the minimum of all the end diastolic values) to 5.84 mm/s (the maximum of all the peak systolic values). With the velocity pulse properly quantified, two parameters can be estimated: (1) the average velocity of the pulse during a cardiac cycle AVV (average velocity value) and (2) the magnitude of the pulsation using Pourcelot's resistive index RI. These parameters are important for the estimation of other hemodynamic parameters such as the average volume flow and the average shear stress. The results of this study revealed that the AVV in the human precapillary arterioles ranged between 0.52 and 3.26 mm/s with a mean value for all microvessels of 1.66 mm/s +/- 0.11 (SE). The RI ranged between 35.5% and 81.8% with a mean value of 53.1%+/- 2.2. Quantitative information was obtained for the first time on the velocity pulse characteristics just before the human capillary bed. (C) 2010 Elsevier Inc. All rights reserved

Volume flow and wall shear stress quantification in the human conjunctival capillaries and post-capillary venules in vivo

Understanding the mathematical relationships of volume blood flow and wall shear stress with respect to microvessel diameter is necessary for the study of vascular design. Here, for the first time, volume flow and wall shear stress were quantified from axial red blood cell velocity measurements in 104 conjunctival microvessels of 17 normal human volunteers. Measurements were taken with a slit lamp based imaging system from the post capillary side of the bulbar conjunctiva in microvessel diameters ranging from 4 to 24 micrometers. The variation of the velocity profile with diameter was taken into account by using a profile factor function. Volume flow ranged from 5 to 462 pl/s with a mean value of 102 pl/s and gave a second power law best fitting line (r = 0.97) deviating significantly from the third power law relation with diameter. The estimated wall shear stress declined hyperbolically (r = 0.93) from a maximum of 9.55 N/m(2) at the smallest capillaries, down to a minimum of 0.28 N/m(2) at the higher diameter post capillary venules. The mean wall shear stress value for all microvessels was 1.54 N/m(2)