["The Journal of Physiology, Volume 604, Issue 7, Page 3077-3093, 1 April 2026. ", "\nAbstract figure legend A, schematic illustration of the ventral aspect of an ex vivo preparation of the entire CNS from a neonatal rat subjected to a calibrated thoracic impact. The trauma induced a large depolarising injury potential (DIP, black trace) recorded from the L5 ventral root (VRrL5), which was markedly reduced by transient receptor potential, vanilloid 4 (TRPV4) antagonism (pink trace). B, motor reflex responses (MMRs) recorded from VRrL5 were abolished at the peak of the DIP as a result of spinal shock but recovered within minutes after trauma. TRPV4 antagonism accelerated this recovery, supporting a protective role for TRPV4 blockade in the immediate aftermath of spinal cord injury.\n\n\n\n\n\n\n\n\nAbstract\nPhysical trauma to the spinal cord causes a massive depolarising injury potential (DIP), transient spinal hypoxia and extensive cell loss at the injury site, disrupting conduction along white matter tracts. This leads to transient hypotonia and areflexia during the spinal shock phase. The link between DIP magnitude and spinal cord injury progression, as well as potential pharmacological interventions, remains unexplored, especially in neonatal age. To limit DIP peak and accelerate motor reflex response (MRR) recovery, we applied selective neurochemicals targeting mechanosensitive and classical neurotransmitter receptors. These agents were applied during experimental trauma to the mid‐thoracic cord of CNS preparations from 0‐ to 2.5‐day‐old rats. Continuous lumbar root recordings monitored baseline levels and MRR elicited by electric pulses to sacro‐caudal afferents. In uninjured preparations, each agent affected baseline polarisation, synaptic responses and bursting activity, indicating their role in maintaining the functional state of the spinal cord. Neurochemicals targeting glutamatergic, adenosinergic, glycinergic or GABAergic receptors did not impact trauma outcomes (DIP or MRR). Only the transient receptor potential, vanilloid 4 (TRPV4) antagonist RN1734, not TRPA1 antagonist AP18, reduced DIP peak and accelerated MRR recovery following trauma. The protective effect of RN1734 was corroborated by TRPV4 expression in neonatal spinal neurons and glial cells, located in dura and around the central canal. Blocking gap junctions and GABAA receptors also restored MRR, but less effectively and more slowly than TRPV4 antagonism. Our findings show that blocking mechanosensitive TRPV4 receptors at the moment of impact effectively reduces the immediate pathological effects of a neonatal spinal trauma.\n\n\n\n\n\n\n\n"]