Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury
Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury
复制标题
DOI：
10.3389/fphar.2016.00047
复制
发表时间：
2016-03-08
影响因子：
5.6
通讯作者：
Esposito, Emanuela
中科院分区：
文献类型：
--
作者：
Crupi, Rosalia;Impellizzeri, Daniela;Esposito, Emanuela
脊髓损伤（SCI）刺激损伤部位星形胶质细胞的活化和免疫细胞的浸润;然而，促进新神经元诞生的机制仍在争论中。脊髓损伤后神经元再生受到限制，但可以通过实验干预刺激。先前我们证明了超微粉化棕榈酰乙醇胺和毛地黄黄酮的共处理，即共-ultraPEALut，减少了炎症。本研究旨在探索co-ultraPEALut在建立的SCI小鼠模型中的神经再生特性。在T5-18处将血管夹应用于脊髓硬脑膜以引起损伤。SCI后每天用co-ultraPEALut（lmg/kg，腹膜内）处理小鼠72小时。Co-ultraPEALut增加了损伤小鼠脊髓中溴脱氧尿苷阳性核和双皮质素免疫反应细胞的数量。为了将神经元发育与突触可塑性联系起来，采用高尔基体方法分析树突棘密度。共-ultraPEALut给药刺激神经营养因子脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子和神经营养因子-3的表达。这些发现显示了co-ultraPEALut给药在新神经元的存活和分化以及脊柱成熟的管理中的显著效果，并且可能代表了脊髓和其他创伤性疾病的治疗性治疗。
Spinal cord injury (SCI) stimulates activation of astrocytes and infiltration of immune cells at the lesion site; however, the mechanism that promotes the birth of new neurons is still under debate. Neuronal regeneration is restricted after spinal cord injury, but can be stimulated by experimental intervention. Previously we demonstrated that treatment co-ultramicronized palmitoylethanolamide and luteolin, namely co-ultraPEALut, reduced inflammation. The present study was designed to explore the neuroregenerative properties of co-ultraPEALut in an estabished murine model of SCI. A vascular clip was applied to the spinal cord dura at T5-18 to provoke injury. Mice were treated with co-ultraPEALut (1 mg/kg, intraperitoneally) daily for 72 h after SCI. Co-ultraPEALut increased the numbers of both bromodeoxyuridine-positive nuclei and doublecortin-immunoreactive cells in the spinal cord of injured mice. To correlate neuronal development with synaptic plasticity a Golgi method was employed to analyze dendritic spine density. Co-ultraPEALut administration stimulated expression of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor, and neurotrophin-3. These findings show a prominent effect of co-ultraPEALut administration in the management of survival and differentiation of new neurons and spine maturation, and may represent a therapeutic treatment for spinal cord and other traumatic diseases.