Spinal cord injury (SCI) is a devastating neurological condition for which there is no effective treatment to restore neurological function. The development of new treatments for those with SCI may be hampered by the insensitivity of clinical tools to assess motor function in humans. Treatments aimed at preserving neuronal function through anti-inflammatory pathways (i.e., neuroprotection) have been a mainstay of pre-clinical SCI research for decades. Minocycline, a clinically available antibiotic agent with anti-inflammatory properties, has demonstrated promising neuroprotective effects in a variety of animal models and improved motor recovery in a Phase-2 human trial. Here, we leveraged our recently developed T3 severe contusion model in the rat to determine the ability of minocycline to preserve descending sympathoexcitatory axons and improve cardiovascular control after SCI. Forty-one male Wistar rats were randomized to either a treatment group (minocycline; n = 20) or a control group (vehicle; n = 21). All rats received a severe T3 contusion. Minocycline (or vehicle) was administered intraperitoneally at one hour post-injury (90 mg/kg), then every 12 h for two weeks (45 mg/kg). Neuroanatomical correlates (lesion area, descending sympathoexcitatory axons) were assessed, in addition to an assessment of cardiovascular control (hemodynamics, autonomic dysreflexia) and motor behavior. Here, we show that minocycline reduces lesion area, increases the number of descending sympathoexctitatory axons traversing the injury site, and ultimately reduces the severity of autonomic dysreflexia. Finally, we show that autonomic dysreflexia is a more sensitive marker of treatment stratification than motor function.

Neurogenic shock, a distributive type of circulatory shock after spinal cord injury (SCI), results in profound hypotension. The consequent hemodynamic instability complicates clinical management, delays surgical intervention, and impacts neurological outcome. Moreover, the reported incidence of this condition varies significantly. We establish the true incidence of neurogenic shock by comparing the most common clinical definitions used to diagnose the condition. Further, we characterize the acute progression and recovery of neurogenic shock. Daily blood pressure, heart rate, and fluid management as well as vasopressor therapy and neurologic status were collected over 30 days from 84 adults admitted to our tertiary trauma center after cervical (n = 56) and thoracic (n = 28) SCI. We found that the reported incidence of neurogenic shock varied greatly depending on which clinical definition was applied. By using a novel combination of hemodynamic and laboratory criteria to define neurogenic shock, the calculated incidence (29% cervical SCI) in our sample most appropriately reflects the true incidence, finding that hypovolemia was the primary factor responsible for the inconsistency in incidence reports between studies. In addition, we found a characteristic decline in blood pressure after the first week post-injury and that fluid management is not currently an integral aspect of clinical management (all persons were treated at a net fluid intake ≤ zero). The results demonstrate the need for accurate identification of neurogenic shock through consistent and appropriate criteria, which is not only important from a clinical point of view, but also in establishing accurate epidemiology to responsibly allocate resources to its management.

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