Table 1 Translational approaches aimed to ameliorate the different elements of psychoneuroimmunoendocrinology in SCI patients
Translational approach | Example | Target | Mechanisms of action and application | References | |
|---|---|---|---|---|---|
Neuroprotective and neuroregenerative agents | 1) Riluzole, hypothermia, GCSF, glibenclamide, minocycline, Cethrin (VX-210), and anti-Nogo-A antibody (neuroprotection) 2) Stem cells (especially mesenchymal stem cells), extracellular vesicles and tissue engineering constructs (neuroregeneration) 3) EES, transcranial and spinal cord magnetic stimulation (neurotechnology) | Spinal cord; central and peripheral nervous system circuits | 1) Neuroprotective agents favorably modulate the spinal cord environment by modulating several pathological processes (i.e., excitotoxicity, oxidative stress, inflammation) thus protecting neurons and glial cells after initial trauma. They should be used as early as possible 2) Neuroregenerative agents are directed to promote the growth and regeneration of nervous tissue by modulating pre-existing cells or creating an environment in which these processes could be favored 3) Neurotechnologies modulate neural networks in the spinal cord through the recruitment of specific circuits to favor different processes (i.e., movements on paralyzed limbs or antispasmodic effects) | ||
Immunomodulatory drugs | 1) MPSS, minocycline (immunosuppressive agents) 2) GCSF, intravenous immunoglobulin G, and monoclonal antibodies against CD11d/CD18, hypothermia and cell transplants using mesenchymal stem cells, TLR2 agonist, CCL2, IL-4 or IL-10 (immunomodulatory approaches) | Directed to modulate the immune system and inflammatory responses | 1) Immunosuppressive agents (specially MPSS) present some controversial results regarding their use, because of the potential pathogenic role of immunodepression in SCI subjects 2) Immunomodulatory drugs offer further advantages due to the dual and complex role of inflammation after SCI. However, further studies understanding the precise role of inflammation and the immune system is required to fulfill adequate immunomodulatory effects for each patient | ||
Endocrine therapy | 1) Steroid hormones (estrogen and testosterone) 2) Thyroid hormones | Ameliorate secondary injury, endocrine dysfunction and impaired metabolism | 1) Estrogens are neuroprotective and immunomodulatory actions in animal models, aiding to ameliorate metabolic dysfunction. Progesterone can synergize with estrogens to limit secondary injury 2) Dihydrotestosterone is effective for attenuating muscle fiber reduction. Further studies are warranted in order to find specific situations in which these therapies may benefit SCI patients | ||
t microbiota modulators | 1) Probiotics (beneficial bacteria), prebiotics (fiber and non-digestible nutrients) and synbiotics (a mixture of pre- and probiotics) 2) FMT | Gut microbiota; MGB axis | 1) Probiotics, prebiotics and synbiotics can be used in the management of urinary tract infections, exerting anti-infectious and immunomodulatory actions. They can also be used for prophylaxis with antibiotics 2) Psychobiotics have the potential to favorably modulate the MGB axis, as well as FMT, which also show promising benefits in ameliorating secondary injury in animal models. However, due to the possibility of significant adverse effects FMT should be further explored before its implementation in clinical routine | [217, 306,307,308,309,310,311,312,313,314,315,316,317,318,319] | |
Psychosomatic interventions | ACT; motivational interviewing; CBT; mentorship experiences; social support; mindfulness-based therapies; philosophical sources (i.e., Stoicism, Buddhism), religious and spiritual beliefs | Psyche; mental well-being | 1) The combination of both clinically relevant treatment strategies with mental health interventions has proven significant benefits for SCI patients, improving functional recovery and quality of life 2) Psychotherapy represents essential support for SCI patients and most interventions are focused on processing emotions and family coping, while educational efforts are mostly directed at coping and adjusting to the new injury | [242, 320,321,322,323,324,325,326,327,328,329,330,331,332,333,334,335,336] | |
Lifestyle medicine | Nutrition | 1) Dietary habits (Mediterranean diet, anti-inflammatory diet) 2) Nutraceuticals (vitamin D, omega-3, creatine, polyphenols from green tea, grapes, olive oil and turmeric) | Pleiotropic effects (Improve neurologic, immunologic, endocrine and metabolic systems, as well as gut microbiota composition and function and the different organs of the body) | 1) Adherence to healthy dietary habits exerts some notable improvements in SCI subjects, especially in combination with low-caloric meals, as this can improve the digestion process due to impaired peristalsis. The combination of diet with other strategies (i.e. when combined with cold) might improve its capacity to control energy balance 2) Nutraceuticals are especially useful in the chronic management of SCI in patients with nutritional deficiencies or in order to ameliorate systemic immune dysfunction and other systemic challenges. Besides they have been explored as promising translational approaches to limiting neurologic damage | [158, 173, 339,340,341,342,343,344,345,346,347,348,349,350,351,352] |
Physical activity | Aerobic and resistance training | Pleiotropic effects (improve neurologic, immunologic, endocrine and metabolic systems, as well as gut microbiota composition and function and the different organs of the body) | 1) Implementation of physical activity as early and with a higher frequency as possible exert significant benefits observed in terms of fitness and health after SCI. SCI patients must be encouraged for sustaining a physically active lifestyle during rehabilitation and each patient may receive and find an adapted and personalized physical training 2) Both aerobic and strength training exert significant benefits in the cardiovascular system and the muscle, as well as in systemic metabolism and mental well-being | ||
Rest and management of sleep | 1) Pharmacological treatment (i.e., melatonin) 2) non-pharmacological approaches (i.e., CBT, relaxation training, sleep restriction, stimulus control therapy and psychoeducation/sleep hygiene rules) | Pleiotropic effects (improve neurologic, immunologic, endocrine and metabolic systems, as well as gut microbiota composition and function and the different organs of the body) | 1) Despite the effectiveness of melatonin to ameliorate sleep disorders in SCI subjects has not been established yet, preclinical studies suggest that melatonin may exert neuroprotective effects and promote the restoration of neurologic function after SCI 2) CBT improves daytime functioning and facilitates adjustment to the therapeutic regimen in patients with SDB and insomnia, whereas other non-pharmacological interventions like respiratory muscle training/exercises, dental appliances or nerve stimulation can be used as alternatives for therapeutic resistance in individuals with SDB | ||