accessing-subdural-space-rodent-spinal-cord-for-treatment

Accessing the Subdural Space of the Rodent Spinal Cord for Treatment Delivery

Treating spinal cord diseases or injuries is challenging, in part, due to difficulties in developing effective treatments that can be directly applied to ...

University of Auckland

Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord's intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential. To address this, we propose a novel intrathecal administration method using an in situ gelling, hyaluronic acid-modified heparin-poloxamer hydrogel loaded with neurotrophin-3 (NT-3) for the direct delivery of NT-3 to the spinal cord. We injected a NT-3 loaded hydrogel into the intrathecal space immediately after contusion SCI in Sprague Dawley (SpD) rats. Our results indicate that injecting the NT-3 loaded hydrogel into the intrathecal space was safe and that the gel was retained alongside the cord for at least one week. Additionally, no adverse effects were observed on rat behaviour. While functional improvement trends were noted, statistical significance was not reached, and immunohistochemistry results showed no significant difference between treatment groups. Overall, our findings suggest the feasibility, safety, and potential of the developed intrathecal administration technique for delivering diverse therapeutic molecules for SCI recovery.

Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury.

Spinal cord injury (SCI) can cause permanent loss of sensory, motor, and autonomic functions, with limited therapeutic options available. Low-frequency electric fields with changing polarity have shown promise in promoting axon regeneration and improving outcomes. However, the metal electrodes used previously were prone to corrosion, and their epidural placement limited the penetration of the electric field into the spinal cord. Here, we demonstrate that a thin-film implant with supercapacitive electrodes placed under the dura mater can safely and effectively deliver electric field treatment in rats with thoracic SCI. Subdural stimulation enhanced hind limb function and touch sensitivity compared to controls, without inducing a neuroinflammatory response in the spinal cord. While axon density around the lesion site remained unchanged after 12 weeks, in vivo monitoring and electrochemical testing of electrodes indicated that treatment was administered throughout the study. These results highlight the promise of electric field treatment as a viable therapeutic strategy for achieving long-term functional recovery in SCI.

Article	Year
Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury. Scientific reports\| PubMed ID: 39455822	2024
Daily electric field treatment improves functional outcomes after thoracic contusion spinal cord injury in rats. Nature communications\| PubMed ID: 40571679	2025

Salvador Lopez

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