Department of Pharmacobiology, Center of Research and Advanced Studies, Mexico City, Mexico.
Unit for Medical Research in Neurological Diseases, National Medical Center, Mexico City, Mexico.
J Neurotrauma. 2020 Dec 1;37(23):2595-2603. doi: 10.1089/neu.2019.6975. Epub 2020 Jul 20.
Severe traumatic brain injury (TBI) results in significant functional disturbances in the hippocampus. Studies support that sodium cromoglycate (CG) induces neuroprotective effects. This study focused on investigating the effects of post-TBI subchronic administration of CG on hippocampal hyperexcitability and damage as well as on sensorimotor impairment in rats. In contrast to the control group (Sham+SS group), animals undergoing severe TBI (TBI+SS group) showed sensorimotor dysfunction over the experimental post-TBI period (day 2, 55%, < 0.001; day 23, 39.5%, < 0.001; day 30, 38.6%, < 0.01). On day 30 post-TBI, TBI+SS group showed neuronal hyperexcitability (63.3%, < 0.01). The hippocampus ipsilateral to the injury showed volume reduction (14.4%, p < 0.001) with a volume of damage of 0.15 ± 0.09 mm. These changes were associated with neuronal loss in the dentate gyrus (ipsilateral, 33%, < 0.05); hilus (ipsilateral, 77%, < 0.001; contralateral, 51%, < 0.001); Cornu Ammonis (CA)1 (ipsilateral, 40%, < 0.01), and CA3 (ipsilateral, 52%, < 0.001; contralateral, 34%, < 0.01). Animals receiving subchronic treatment with CG (50 mg/kg, s.c. daily for 10 days) after TBI (TBI+CG group) displayed a sensorimotor dysfunction less evident than that of the TBI+SS group ( < 0.001). Their hippocampal excitability was similar to that of the Sham+SS group ( = 0.21). The TBI+CG group presented hippocampal volume reduction (12.7%, = 0.94) and damage (0.10 ± 0.03 mm, > 0.99) similar to the TBI+SS group. However, their hippocampal neuronal preservation was similar to that of the Sham+SS group. These results indicate that CG represents an appropriate and novel pharmacological strategy to reduce the long-term sensorimotor impairment and hippocampal damage and hyperexcitability that result as consequences of severe TBI.
严重创伤性脑损伤 (TBI) 会导致海马体的功能严重障碍。研究表明，色甘酸钠 (CG) 具有神经保护作用。本研究重点研究 TBI 后亚慢性给予 CG 对大鼠海马体过度兴奋和损伤以及感觉运动障碍的影响。与对照组（Sham+SS 组）相比，经历严重 TBI 的动物（TBI+SS 组）在 TBI 后的实验期间表现出感觉运动功能障碍（第 2 天，55%， < 0.001；第 23 天，39.5%， < 0.001；第 30 天，38.6%， < 0.01）。在 TBI 后第 30 天，TBI+SS 组表现出神经元过度兴奋（63.3%， < 0.01）。损伤对侧海马体体积减小（14.4%，p < 0.001），损伤体积为 0.15 ± 0.09 mm。这些变化与齿状回（同侧，33%， < 0.05）；门区（同侧，77%， < 0.001；对侧，51%， < 0.001）；Cornu Ammonis（CA）1（同侧，40%， < 0.01）和 CA3（同侧，52%， < 0.001；对侧，34%， < 0.01）的神经元丢失有关。TBI 后接受亚慢性 CG 治疗（50 mg/kg，每天皮下注射 10 天）的动物（TBI+CG 组）表现出的感觉运动功能障碍比 TBI+SS 组不那么明显（ < 0.001）。它们的海马兴奋性与 Sham+SS 组相似（ = 0.21）。TBI+CG 组海马体体积减小（12.7%， = 0.94）和损伤（0.10 ± 0.03 mm， > 0.99）与 TBI+SS 组相似。然而，它们的海马神经元保存与 Sham+SS 组相似。这些结果表明，CG 是一种合适的新型药理学策略，可以减少严重 TBI 后导致的长期感觉运动障碍和海马体损伤及过度兴奋。
