Mechanical Heterogeneity of the Rat Hippocampus Measured by Atomic Force Microscope Indentation

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Abstract
Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about traumatic brain injury (TBI) mechanisms and for accurate TBI simulations. To determine the local mechanical properties of anatomical subregions within the rat hippocampus, the atomic force microscope (AFM) was adapted for use on living brain tissue. The AFM provided advantages over alternative methods for measuring local mechanical properties of brain because of its high spatial resolution, high sensitivity, and ability to measure live samples under physiologic conditions. From AFM indentations, a mean pointwise or depth-dependent apparent elastic modulus, Ě, was determined for the following hippocampal subregions: CA1 pyramidal cell layer (CA1P) and stratum radiatum (CA1SR), CA3 pyramidal cell layer (CA3P) and stratum radiatum (CA3SR), and the dentate gyrus (DG). For all regions, Ě was indentation-depth-dependent, reflecting the nonlinearity of brain tissue. At an indentation depth of 3 μm, Ě was 234 ± 152 Pa for CA3P, 308 ± 184 Pa for CA3SR, 137 ± 97 Pa for CA1P, 169 ± 52 Pa for CA1SR, and 201 ± 133 Pa for DG (mean ± SD). Our results demonstrate for the first time that the hippocampus is mechanically heterogeneous. Based on our findings, we discuss hypotheses accounting for experimentally observed patterns of hippocampal cell death, which can be tested with biofidelic finite element models of TBI.