Brain stiffens post mortem

Abstract

Alterations in brain rheology are increasingly recognized as a diagnostic marker for various neurological conditions. Magnetic resonance elastography now allows us to assess brain rheology repeatably, reproducibly, and non-invasively in vivo. Recent elastography studies suggest that brain stiffness decreases one percent per year during normal aging, and is significantly reduced in Alzheimer's disease and multiple sclerosis. While existing studies successfully compare brain stiffnesses across different populations, they fail to provide insight into changes within the same brain. Here we characterize rheological alterations in one and the same brain under extreme metabolic changes: alive and dead. Strikingly, the storage and loss moduli of the cerebrum increased by 26% and 60% within only three minutes post mortem and continued to increase by 40% and 103% within 45 minutes. Immediate post mortem stiffening displayed pronounced regional variations; it was largest in the corpus callosum and smallest in the brainstem. We postulate that post mortem stiffening is a manifestation of alterations in polarization, oxidation, perfusion, and metabolism immediately after death. Our results suggest that the stiffness of our brain-unlike any other organ-is a dynamic property that is highly sensitive to the metabolic environment. Our findings emphasize the importance of characterizing brain tissue in vivo and question the relevance of ex vivo brain tissue testing as a whole. Knowing the true stiffness of the living brain has important consequences in diagnosing neurological conditions, planning neurosurgical procedures, and modeling the brain's response to high impact loading.

Zebrafish spinal cord repair is accompanied by transient tissue stiffening

“…Gefen and Margulies, for instance, showed that the mechanical properties of brain tissue in vivo differ from excised tissue only after repetitive, but not at the first indentation [48]. Weickenmeier et al used magnetic resonance elastography and showed that brain tissue rapidly stiffens after death [49]. As it is currently unclear how in vivo mechanical properties change post mortem, mechanical tissue properties must be measured in vivo to rule out any effects elicited by the death of the animal.…”

Functional hyperemia drives fluid exchange in the paravascular space

“…When the brain is presumed rigid, our simulations show that the peak pressures in the PVS during pulsations can reach 3 mmHg (Fig 2c). Given that the brain is a soft tissue with a shear modulus in the range of 1-8 kPa [16][17][18][19] , we estimated that the peak displacement of the brain tissue induced by the pressure profile in Fig 2c would be 0.64m (with a shear modulus of 4 kPa). This displacement value stands in stark contrast to the fact that the arterial wall displacement driving the flow is only 0.06m.…”

“…The radius of the simulated section of brain tissue was taken to be in the range of 100-200 m, half of the typical distance between two penetrating arteries in the mouse cortex 84,85 . The elastic (shear) modulus of the brain tissue is taken to be between 1-8 kPa, spanning the values found in the literature [16][17][18][19]71,72,86,87 .…”

“…Moreover, the previously published models have treated the brain tissue as a rigid solid for simplicity. In reality, brain tissue is very compliant [16][17][18][19] ('soft'), with a shear modulus in the range of 1-8kPa. While a few models of fluid flow in the brain have considered physiological constraints on pressure differences 12 , none have sought to incorporate tissue deformation in response to the variation in pressure.…”

“…While a few models of fluid flow in the brain have considered physiological constraints on pressure differences 12 , none have sought to incorporate tissue deformation in response to the variation in pressure. Given the compliant nature of the brain [16][17][18][19] , even relatively small pressure changes will cause deformations of the tissue and would consequently produce fluid movements very different from those that would occur if the brain were rigid.…”