Department of Pediatric, The First People's Hospital of Taizhou, 318020 Taizhou, Zhejiang, China.
Discov Med. 2024 Aug;36(187):1588-1599. doi: 10.24976/Discov.Med.202436187.145.
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.
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 () mRNA expression and western blot for VEGF protein expression were used for evaluated angiogenesis.
The administration of RF could facilitate the recovery of neurological function by promoting the recovery of sensorimotor function and cognitive ability ( < 0.05). Furthermore, RF could reduce the lesion volume and water content after TBI and ameliorate neural apoptosis, neuroinflammation, and oxidative stress ( < 0.05). Finally, RF increased vessel density ( < 0.01) and levels ( < 0.01) in brain tissues after TBI, promoting angiogenesis.
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.
创伤性脑损伤（TBI）是由外力损伤头部和大脑引起的脑损伤和病变，可导致儿科死亡、残疾、神经障碍，甚至终身残疾。本研究旨在探讨核黄素（RF）对 TBI 后神经康复和功能恢复的影响。
采用皮质控制撞击（CCI）法构建 TBI 大鼠模型。通过用 RF 处理 TBI 大鼠，我们通过粘取试验、改良神经严重程度评分（mNSS）、转角试验、线抓试验和 Morris 水迷宫来研究 RF 的给药是否会影响感觉运动功能和认知能力的恢复。通过苏木精和伊红（H&E）染色和干湿法研究 RF 对病变体积和含水量的影响。通过尼氏染色和末端脱氧核苷酸转移酶（TdT）介导的 dUTP 缺口末端标记（TUNEL）染色来证明 RF 对神经细胞凋亡的影响。通过酶联免疫吸附试验（ELISA）测定白细胞介素（IL）-6、IL-1β、肿瘤坏死因子（TNF）-α和转化生长因子（TGF）-β1 等炎症相关细胞因子，以评估 RF 对神经炎症的影响。通过测量丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性来评估 RF 对氧化应激的影响，通过血小板内皮细胞黏附分子-1（CD31）染色观察血管密度，通过逆转录定量实时聚合酶链反应（RT-qPCR）测量血管内皮生长因子（）mRNA 表达，通过蛋白质印迹法测量 VEGF 蛋白表达，以评估血管生成。
RF 的给药可以通过促进感觉运动功能和认知能力的恢复来促进神经功能的恢复（<0.05）。此外，RF 可以减少 TBI 后的病变体积和含水量，并改善神经细胞凋亡、神经炎症和氧化应激（<0.05）。最后，RF 增加了 TBI 后脑组织中的血管密度（<0.01）和水平（<0.01），促进了血管生成。
RF 通过促进神经功能恢复、改善 TBI 后的发病机制和促进脑血管重塑，有益于 TBI 后的神经康复。这些发现为 RF 治疗儿科 TBI 提供了一种新的机制。
