Serum BDNF Levels Are Reduced in Patients with Disorders of Consciousness and Are Not Modified by Verticalization with Robot-Assisted Lower-Limb Training
Sergio Bagnato, Giuseppe Galardi, Francesco Ribaudo, Cristina Boccagni, Teresa Fiorilla, Francesca Rubino, Maria Enza D’Ippolito, Maria Andriolo
Abstract
Little is known about plastic changes occurring in the brains of patients with severe disorders of consciousness (DOCs) caused by acute brain injuries at rest and during rehabilitative treatment. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity whose production is powerfully modulated by physical exercise. In this study, we compared serum BDNF levels in 18 patients with unresponsive wakefulness syndrome (UWS) and in a minimally conscious state (MCS) with those in 16 sex- and age-matched healthy controls. In 12 patients, serum BDNF levels before and after verticalization with ErigoPro robot-assisted lower-limb training were compared. Serum BDNF levels were significantly lower in patients (median, 1141 pg/ml; 25 th and 75 th percentiles, 1016 and 1704 pg/ml) than in controls (median, 2450 pg/ml; 25 th and 75 th percentiles, 2100 and 2875 pg/ml; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>). BDNF levels measured before and after verticalization with robot-assisted lower-limb training did not change (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.5</mml:mn></mml:math>). Moreover, BDNF levels did not differ between patients with UWS and MCS (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.2</mml:mn></mml:math>), or between patients with traumatic and nontraumatic brain injuries (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.6</mml:mn></mml:math>). BDNF level correlated positively with the time since brain injury (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.025</mml:mn></mml:math>). In conclusion, serum BDNF levels are reduced in patients with UWS and MCS and cannot be improved by verticalization associated with passive lower-limb training. Additional studies are needed to better understand the mechanisms underlying BDNF reduction in patients with DOCs and to determine the best rehabilitative strategies to promote restorative plastic changes in these patients.