The Effect of Riboflavin on Neurological Rehabilitation after Traumatic Brain Injury in Children.

Background: Traumatic brain injury (TBI), which is the brain impairment and lesion caused by the external force injuring the head and the underlying brain, can cause pediatric death, disability, neurological disorders, and even lifelong disability. This study was to explore the effect of riboflavin (RF) on neurological rehabilitation and functional recovery after TBI.

Methods: The rat models of TBI were constructed by treating rats with controlled cortical impact (CCI). By treating TBI rats with RF, we investigated whether the administration of RF would affect the sensorimotor function and cognitive ability recovery through adhesive removal test, modified neurological severity score (mNSS), corner test, wire-grip test and the Morris water maze. The effects of RF on lesion volume and water content were investigated using hematoxylin and eosin (H&E) staining and wet-dry method. The Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to demonstrate the effect of RF on neural apoptosis. Inflammation-related cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RF on neuroinflammation. The impact of RF on oxidative stress was assessed by measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and the platelet endothelial cell adhesion molecule-1 (CD31) staining for observing vessel density, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for measuring vascular endothelial growth factor (VEGF) mRNA expression and western blot for VEGF protein expression were used for evaluated angiogenesis.

Results: The administration of RF could facilitate the recovery of neurological function by promoting the recovery of sensorimotor function and cognitive ability (p < 0.05). Furthermore, RF could reduce the lesion volume and water content after TBI and ameliorate neural apoptosis, neuroinflammation, and oxidative stress (p < 0.05). Finally, RF increased vessel density (p < 0.01) and VEGF levels (p < 0.01) in brain tissues after TBI, promoting angiogenesis.

Conclusion: RF benefits neurological rehabilitation after TBI by promoting neurological function recovery, ameliorating the pathogenesis after TBI, and facilitating brain vascular remodeling. These findings provide a novel mechanism for RF treating pediatric TBI.