Controlled delivery of a neurotransmitter–agonist conjugate for functional recovery after severe spinal cord injury – Nature Nanotechnology

David, S. & Kroner, A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat. Rev. Neurosci. 12, 388–399 (2011).

Article  CAS  Google Scholar 

Block, M. L., Zecca, L. & Hong, J. S. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57–69 (2007).

Article  CAS  Google Scholar 

Ulndreaj, A., Badner, A. & Fehlings, M. G. Promising neuroprotective strategies for traumatic spinal cord injury with a focus on the differential effects among anatomical levels of injury. F1000Research 6, 1907 (2017).

Article  Google Scholar 

Li, L. et al. A MnO₂ nanoparticle-dotted hydrogel promotes spinal cord repair via regulating reactive oxygen species microenvironment and synergizing with mesenchymal stem cells. ACS Nano 13, 14283–14293 (2019).

Article  CAS  Google Scholar 

Zhang, N. et al. A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury. Adv. Sci. 8, e2100805 (2021).

Article  Google Scholar 

Chen, B. et al. Reactivation of dormant relay pathways in injured spinal cord by KCC2 manipulations. Cell 174, 521–535.e13 (2018).

Article  CAS  Google Scholar 

Wilson, J. M., Blagovechtchenski, E. & Brownstone, R. M. Genetically defined inhibitory neurons in the mouse spinal cord dorsal horn: a possible source of rhythmic inhibition of motoneurons during fictive locomotion. J. Neurosci. 30, 1137–1148 (2010).

Article  CAS  Google Scholar 

Haring, M. et al. Neuronal atlas of the dorsal horn defines its architecture and links sensory input to transcriptional cell types. Nat. Neurosci. 21, 869–880 (2018).

Article  Google Scholar 

Brommer, B. et al. Improving hindlimb locomotor function by non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury. Nat. Commun. 12, 781 (2021).

Article  CAS  Google Scholar 

Courtine, G. & Sofroniew, M. V. Spinal cord repair: advances in biology and technology. Nat. Med. 25, 898–908 (2019).

Article  CAS  Google Scholar 

Ramirez-Jarquin, U. N., Lazo-Gomez, R., Tovar, Y. R. L. B. & Tapia, R. Spinal inhibitory circuits and their role in motor neuron degeneration. Neuropharmacology 82, 101–107 (2014).

Article  CAS  Google Scholar 

Matsuya, R., Ushiyama, J. & Ushiba, J. Inhibitory interneuron circuits at cortical and spinal levels are associated with individual differences in corticomuscular coherence during isometric voluntary contraction. Sci. Rep. 7, 44417 (2017).

Article  CAS  Google Scholar 

Ramirez-Jarquin, U. N. & Tapia, R. Excitatory and inhibitory neuronal circuits in the spinal cord and their role in the control of motor neuron function and degeneration. ACS Chem. Neurosci. 9, 211–216 (2018).

Article  CAS  Google Scholar 

Rivera, C. et al. The K⁺/Cl^– co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397, 251–255 (1999).

Article  CAS  Google Scholar 

Boulenguez, P. et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat. Med. 16, 302–307 (2010).

Article  CAS  Google Scholar 

Gagnon, M. et al. Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat. Med. 19, 1524–1528 (2013).

Article  CAS  Google Scholar 

Reinig, S., Driever, W. & Arrenberg, A. B. The descending diencephalic dopamine system is tuned to sensory stimuli. Curr. Biol. 27, 318–333 (2017).

Article  CAS  Google Scholar 

Li, Y. et al. Pericytes impair capillary blood flow and motor function after chronic spinal cord injury. Nat. Med. 23, 733–741 (2017).

Article  CAS  Google Scholar 

Sharples, S. A. et al. A dynamic role for dopamine receptors in the control of mammalian spinal networks. Sci. Rep. 10, 16429 (2020).

Article  Google Scholar 

Grillner, S. & Jessell, T. M. Measured motion: searching for simplicity in spinal locomotor networks. Curr. Opin. Neurobiol. 19, 572–586 (2009).

Article  CAS  Google Scholar 

Li, W. C. & Moult, P. R. The control of locomotor frequency by excitation and inhibition. J. Neurosci. 32, 6220–6230 (2012).

Article  CAS  Google Scholar 

Kiehn, O. Decoding the organization of spinal circuits that control locomotion. Nat. Rev. Neurosci. 17, 224–238 (2016).

Article  CAS  Google Scholar 

Jiang, X. C. et al. Neural stem cells transfected with reactive oxygen species–responsive polyplexes for effective treatment of ischemic stroke. Adv. Mater. 31, e1807591 (2019).

Article  Google Scholar 

Liu, P. et al. Biomimetic dendrimer–peptide conjugates for early multi-target therapy of Alzheimer’s disease by inflammatory microenvironment modulation. Adv. Mater. 33, e2100746 (2021).

Article  Google Scholar 

Lu, Y. et al. Microenvironment remodeling micelles for Alzheimer’s disease therapy by early modulation of activated microglia. Adv. Sci. 6, 1801586 (2019).

Article  Google Scholar 

Xu, W. et al. Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord 43, 204–213 (2005).

Article  CAS  Google Scholar 

Zhang, M. et al. Oxidation and temperature dual responsive polymers based on phenylboronic acid and N-isopropylacrylamide motifs. Polym. Chem. 7, 1494–1504 (2016).

Article  CAS  Google Scholar 

Lin, L. et al. Nanodrug with ROS and pH dual-sensitivity ameliorates liver fibrosis via multicellular regulation. Adv. Sci. 7, 1903138 (2020).

Article  CAS  Google Scholar 

Zhang, D., Fan, Y., Chen, H., Trepout, S. & Li, M. H. CO₂-activated reversible transition between polymersomes and micelles with AIE fluorescence. Angew. Chem. Int. Ed. 58, 10260–10265 (2019).

Article  CAS  Google Scholar 

Suk, J. S., Xu, Q., Kim, N., Hanes, J. & Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 99, 28–51 (2016).

Article  CAS  Google Scholar 

Hu, J. et al. Long circulating polymeric nanoparticles for gene/drug delivery. Curr. Drug Metab. 19, 723–738 (2018).

Article  CAS  Google Scholar 

Zhang, Z. et al. Circulatory disturbance of rat spinal cord induced by occluding ligation of the dorsal spinal vein. Acta Neuropathol. 102, 335–338 (2001).

Article  CAS  Google Scholar 

Farrar, M. J., Rubin, J. D., Diago, D. M. & Schaffer, C. B. Characterization of blood flow in the mouse dorsal spinal venous system before and after dorsal spinal vein occlusion. J. Cereb. Blood Flow. Metab. 35, 667–675 (2015).

Article  Google Scholar 

Bartanusz, V., Jezova, D., Alajajian, B. & Digicaylioglu, M. The blood–spinal cord barrier: morphology and clinical implications. Ann. Neurol. 70, 194–206 (2011).

Article  Google Scholar 

Jin, L. Y. et al. Blood–spinal cord barrier in spinal cord injury: a review. J. Neurotrauma 38, 1203–1224 (2021).

Article  Google Scholar 

Zrzavy, T. et al. Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury. Brain 144, 144–161 (2021).

Article  Google Scholar 

Cooney, S. J., Zhao, Y. & Byrnes, K. R. Characterization of the expression and inflammatory activity of NADPH oxidase after spinal cord injury. Free Radic. Res. 48, 929–939 (2014).

Article  CAS  Google Scholar 

Bakh, N. A. et al. Glucose-responsive insulin by molecular and physical design. Nat. Chem. 9, 937–943 (2017).

Article  CAS  Google Scholar 

Chou, D. H. et al. Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates. Proc. Natl Acad. Sci. USA 112, 2401–2406 (2015).

Article  CAS  Google Scholar 

Ahuja, C. S. et al. Traumatic spinal cord injury. Nat. Rev. Dis. Prim. 3, 17018 (2017).

Article  Google Scholar 

Li, X. et al. The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord. Biomaterials 245, 119978 (2020).

Article  CAS  Google Scholar 

Schucht, P., Raineteau, O., Schwab, M. E. & Fouad, K. Anatomical correlates of locomotor recovery following dorsal and ventral lesions of the rat spinal cord. Exp. Neurol. 176, 143–153 (2002).

Article  CAS  Google Scholar 

Qiao, Y. et al. Spinal dopaminergic mechanisms regulating the micturition reflex in male rats with complete spinal cord injury. J. Neurotrauma 38, 803–817 (2021).

Article  Google Scholar 

Shi, Y. et al. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles. Nat. Nanotechnol. 5, 80–87 (2010).

Article  CAS  Google Scholar 

Ye, J. et al. Rationally designed, self-assembling, multifunctional hydrogel depot repairs severe spinal cord injury. Adv. Health. Mater. 10, e2100242 (2021).

Article  Google Scholar 

Watson, C. et al. in The Spinal Cord Ch 15 (Academic Press, 2008).

Hong, L. T. A. et al. An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling. Nat. Commun. 8, 533 (2017).

Article  Google Scholar 

Basso, D. M., Beattie, M. S. & Bresnahan, J. C. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp. Neurol. 139, 244–256 (1996).

Article  CAS  Google Scholar 

Wenger, N. et al. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury. Nat. Med. 22, 138–145 (2016).

Article  CAS  Google Scholar