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Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1 (PRIP1-/- mice) display anxiety-like behavior and altered γ-aminobutyric acid (GABA)A-receptor pharmacology. Here, we examined associations between anxiety and motor-function recovery in PRIP1-/- mice after a spinal cord injury (SCI) induced by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/- mice showed less distance than wild-type (WT) mice in the center 25% in an open field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in both WT and PRIP1-/- mice after SCI. WT and PRIP1-/- mice were completely paralyzed on day 1 after SCI, but gradually recovered until reaching a plateau at ∼4 weeks. After SCI, the PRIP1-/- mice had significantly greater motor dysfunction than the WT mice. In WT mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and velocity, and with the reaction time in a plantar pressure-sensitivity mechanical test. In PRIP1-/- mice after SCI, the percentage of distance spent in the center 25% of the OFT was correlated with the OFT distance traveled and with the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) expressions were elevated at the lesion epicenter in PRIP1-/- mice, and spinal cord atrophy and demyelination were more severe than in WT mice. The axonal fiber development was also decreased in PRIP1-/- mice, consistent with the poor motor-function recovery after SCI in these mice.

An injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fold larger than in controls. With NHC treatment, tissue in the injury had a 2-fold higher M2/M1 macrophage ratio, 5-fold higher blood vessel density, 2.6-fold higher immature neuron presence, 2.4-fold higher axon density, and a similar glial scar presence compared with controls. However, the spared nervous tissue volume in the contused segment and hind limb function was similar between groups. Our findings indicated that NHC provided mechanical support to the contused spinal cord and supported pro-regenerative macrophage polarization, angiogenesis, axon growth, and neurogenesis in the injured tissue without any exogenous factors or cells. These results motivate further optimization NHC and delivery protocol to fully translate the potential of the unique properties of NHC for treating spinal cord injury.