Baloğlu M, Gökalp Özkorkmaz E
Department of Physiotherapy, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkey.
Department of Histology and Embryology, Dicle University, School of Medicine, Diyarbakır, Turkey.
Folia Morphol (Warsz). 2019;78(4):676-683. doi: 10.5603/FM.a2019.0036. Epub 2019 Apr 5.
Lesion in spinal cord causes a cascade of events such as the apoptosis of neurons and eventually, neurological dysfunction. Neurologic damage developing after acute spinal cord injury is also related with necrosis and free radical formation. Allopurinol, a xanthine oxidase inhibitor, was shown to have protective effects in several studies. B-cell lymphoma 2 (Bcl-2) family proteins regulate apoptosis. Apoptosis causes the death of neuronal cells, particularly neurons and oligodendrocytes in the spinal cord after lesion. Glial fibrillary acidic protein (GFAP) takes part in astrocyte and neuronal interconnection and synaptic transmission.
Male Sprague Dawley rats (n = 30) were divided as control, trauma, and trauma + allopurinol (i.p., 50 mg/kg of body weight) groups. Animals were applied a surgical procedure causing spinal cord injury and treated for 7 days then sacrificed under anaesthesia. The spinal cords were dissected, measurements of myeloperoxidase, malondialdehyde and glutathione were performed, remaining parts were fixed in 10% formaldehyde solution for histological and immunohistochemical evaluations.
Biochemical results exhibited an increase in myeloperoxidase levels in trauma group but a decrease in the allopurinol treatment group similar to malondialdehyde levels. Degenerative changes in multipolar and bipolar neurons together with apoptotic changes in some glial cells were observed in the trauma group whereas, mild degenerative changes were observed after allopurinol treatment. In the trauma group, negative GFAP expression in multipolar versus bipolar neuronal processes with a reduction in glial processes around blood vessels and positive GFAP expression were observed but, a regular and parallel positive GFAP expression of glial processes around blood vessels in the allopurinol treated group was apparent. Trauma group depicted a positive Bcl-2 expression in glial cells and in motor and bipolar neurons. On the contrary, negative Bcl-2 expression was noticed in the trauma + allopurinol group.
This study is of importance to understand the effects of allopurinol in preventing degenerative changes in nerve and glial cells related to spinal cord injuries.
脊髓损伤会引发一系列事件，如神经元凋亡，最终导致神经功能障碍。急性脊髓损伤后发生的神经损伤也与坏死和自由基形成有关。在多项研究中，黄嘌呤氧化酶抑制剂别嘌醇显示出具有保护作用。B细胞淋巴瘤2（Bcl-2）家族蛋白调节细胞凋亡。细胞凋亡会导致神经元细胞死亡，特别是脊髓损伤后脊髓中的神经元和少突胶质细胞。胶质纤维酸性蛋白（GFAP）参与星形胶质细胞与神经元的相互连接以及突触传递。
将30只雄性Sprague Dawley大鼠分为对照组、创伤组和创伤+别嘌醇组（腹腔注射，50mg/kg体重）。对动物实施导致脊髓损伤的外科手术，并治疗7天，然后在麻醉下处死。解剖脊髓，检测髓过氧化物酶、丙二醛和谷胱甘肽，其余部分固定在10%甲醛溶液中进行组织学和免疫组织化学评估。
生化结果显示，创伤组髓过氧化物酶水平升高，而别嘌醇治疗组与丙二醛水平相似有所降低。创伤组观察到多极和双极神经元的退行性变化以及一些神经胶质细胞的凋亡变化，而别嘌醇治疗后观察到轻度退行性变化。在创伤组中，多极与双极神经元突起中GFAP表达阴性，血管周围神经胶质突起减少且GFAP表达阳性，但在别嘌醇治疗组中，血管周围神经胶质突起呈现规则且平行的GFAP阳性表达。创伤组在神经胶质细胞以及运动和双极神经元中显示Bcl-2阳性表达。相反，创伤+别嘌醇组中观察到Bcl-2阴性表达。
本研究对于理解别嘌醇在预防与脊髓损伤相关的神经和神经胶质细胞退行性变化方面的作用具有重要意义。
