Biophysics of Computation

The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n = 192 indentation tests We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem White matter, with an average modulus of 1895 kPa±0592 kPa, was on average 39% stiffer than gray matter, p 001 , with an average modulus of 1389 kPa±0289 kPa, and displayed larger regional variations It was also more viscous than gray matter and responded less rapidly to mechanical loading Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders

Mechanical properties of gray and white matter brain tissue by indentation.

Implantable neuroprostheses are engineered systems designed to restore or substitute function for individuals with neurological deficits or disabilities. These systems involve at least one uni- or bidirectional interface between a living neural tissue and a synthetic structure, through which information in the form of electrons, ions or photons flows. Despite a few notable exceptions, the clinical dissemination of implantable neuroprostheses remains limited, because many implants display inconsistent long-term stability and performance, and are ultimately rejected by the body. Intensive research is currently being conducted to untangle the complex interplay of failure mechanisms. In this Review, we emphasize the importance of minimizing the physical and mechanical mismatch between neural tissues and implantable interfaces. We explore possible materials solutions to design and manufacture neurointegrated prostheses, and outline their immense therapeutic potential. Implantable neuroprostheses communicate with the nervous system to provide diagnosis or therapy to the injured body. In this review, we discuss materials-based approaches to overcome the physical and mechanical mismatch at the tissue–implant interface and to design long-term neurointegrated prostheses.

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Materials and technologies for soft implantable neuroprostheses

Mechanical characterization of human brain tissue.

The human brain is the organ with the highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that the basement membranes of cerebral capillaries and arteries represent the lymphatic pathways of the brain along which intramural periarterial drainage (IPAD) of soluble metabolites occurs. Failure of IPAD could explain the vascular deposition of the amyloid-beta protein as cerebral amyloid angiopathy (CAA), which is a key pathological feature of Alzheimer's disease. The underlying mechanisms of IPAD, including its motive force, have not been clarified, delaying successful therapies for CAA. Although arterial pulsations from the heart were initially considered to be the motive force for IPAD, they are not strong enough for efficient IPAD. This study aims to unravel the driving force for IPAD, by shifting the perspective of a heart-driven clearance of soluble metabolites from the brain to an intrinsic mechanism of cerebral arteries (e.g., vasomotion-driven IPAD). We test the hypothesis that the cerebrovascular smooth muscle cells, whose cycles of contraction and relaxation generate vasomotion, are the drivers of IPAD. A novel multiscale model of arteries, in which we treat the basement membrane as a fluid-filled poroelastic medium deformed by the contractile cerebrovascular smooth muscle cells, is used to test the hypothesis. The vasomotion-induced intramural flow rates suggest that vasomotion-driven IPAD is the only mechanism postulated to date capable of explaining the available experimental observations. The cerebrovascular smooth muscle cells could represent valuable drug targets for prevention and early interventions in CAA.

/pdf/cerebrovascular-smooth-muscle-cells-as-the-drivers-of-3jc4r4jgeb.pdf

Cerebrovascular Smooth Muscle Cells as the Drivers of Intramural Periarterial Drainage of the Brain

The human brain is the continuous subject of extensive investigation aimed at understanding its behavior and function. Despite a clear evidence that mechanical factors play an important role in regulating brain activity, current research efforts focus mainly on the biochemical or electrophysiological activity of the brain. Here, we show that classical mechanical concepts including deformations, stretch, strain, strain rate, pressure, and stress play a crucial role in modulating both brain form and brain function. This opinion piece synthesizes expertise in applied mathematics, solid and fluid mechanics, biomechanics, experimentation, material sciences, neuropathology, and neurosurgery to address today’s open questions at the forefront of neuromechanics. We critically review the current literature and discuss challenges related to neurodevelopment, cerebral edema, lissencephaly, polymicrogyria, hydrocephaly, craniectomy, spinal cord injury, tumor growth, traumatic brain injury, and shaken baby syndrome. The multi-disciplinary analysis of these various phenomena and pathologies presents new opportunities and suggests that mechanical modeling is a central tool to bridge the scales by synthesizing information from the molecular via the cellular and tissue all the way to the organ level.

/pdf/mechanics-of-the-brain-perspectives-challenges-and-3ercw4qnop.pdf

Jaw Hans van Dommelen

Papers

Mechanics of the brain: perspectives, challenges, and opportunities