Butler Max B, Vellaiyappan Sundar K, Bhatti Faheem, Syed Fazal-E-Momin, Rafati Fard Amir, Teh Jye Quan, Grodzinski Ben, Akhbari Melika, Adeeko Sylva, Dilworth Rory, Bhatti Aniqah, Waheed Unaiza, Robinson Sophie, Osunronbi Temidayo, Walker Benn, Ottewell Luke, Suresh Gayathri, Kuhn Isla, Davies Benjamin M, Kotter Mark R N, Mowforth Oliver D
Division of Academic Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
Medical Library, University of Cambridge, Cambridge, United Kingdom.
Front Med (Lausanne). 2023 Aug 22;10:1237219. doi: 10.3389/fmed.2023.1237219. eCollection 2023.
Systematic review.
The objective of this study was to evaluate the impact of phosphodiesterase (PDE) inhibitors on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury (SCI).
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered with PROSPERO (CRD42019150639). Searches were performed in MEDLINE and Embase. Studies were included if they evaluated the impact of PDE inhibitors on neurobehavioral outcomes in preclinical models of traumatic or non-traumatic SCI. Data were extracted from relevant studies, including sample characteristics, injury model, and neurobehavioral assessment and outcomes. Risk of bias was assessed using the SYRCLE checklist.
The search yielded a total of 1,679 studies, of which 22 met inclusion criteria. Sample sizes ranged from 11 to 144 animals. PDE inhibitors used include rolipram ( = 16), cilostazol ( = 4), roflumilast ( = 1), and PDE4-I ( = 1). The injury models used were traumatic SCI ( = 18), spinal cord ischemia ( = 3), and degenerative cervical myelopathy ( = 1). The most commonly assessed outcome measures were Basso, Beattie, Bresnahan (BBB) locomotor score ( = 13), and grid walking ( = 7). Of the 22 papers that met the final inclusion criteria, 12 showed a significant improvement in neurobehavioral outcomes following the use of PDE inhibitors, four papers had mixed findings and six found PDE inhibitors to be ineffective in improving neurobehavioral recovery following an SCI. Notably, these findings were broadly consistent across different PDE inhibitors and spinal cord injury models.
In preclinical models of traumatic and non-traumatic SCI, the administration of PDE inhibitors appeared to be associated with statistically significant improvements in neurobehavioral outcomes in a majority of included studies. However, the evidence was inconsistent with a high risk of bias. This review provides a foundation to aid the interpretation of subsequent clinical trials of PDE inhibitors in spinal cord injury.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150639, identifier: CRD42019150639.
系统评价。
本研究的目的是评估磷酸二酯酶（PDE）抑制剂对创伤性和非创伤性脊髓损伤（SCI）临床前模型神经行为结果的影响。
按照系统评价和Meta分析的首选报告项目（PRISMA）指南进行系统评价，并在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42019150639）进行注册。在MEDLINE和Embase数据库中进行检索。纳入评估PDE抑制剂对创伤性或非创伤性SCI临床前模型神经行为结果影响的研究。从相关研究中提取数据，包括样本特征、损伤模型以及神经行为评估和结果。使用SYRCLE清单评估偏倚风险。
检索共得到1679项研究，其中22项符合纳入标准。样本量从11只到144只动物不等。使用的PDE抑制剂包括咯利普兰（n = 16）、西洛他唑（n = 4）、罗氟司特（n = 1）和PDE4抑制剂（n = 1）。使用的损伤模型为创伤性SCI（n = 18）、脊髓缺血（n = 3）和退行性颈椎病（n = 1）。最常评估的结果指标是Basso、Beattie、Bresnahan（BBB）运动评分（n = 13）和网格行走测试（n = 7）。在符合最终纳入标准的22篇论文中，12篇显示使用PDE抑制剂后神经行为结果有显著改善，4篇研究结果不一，6篇发现PDE抑制剂在改善SCI后的神经行为恢复方面无效。值得注意的是，这些发现对于不同的PDE抑制剂和脊髓损伤模型具有广泛的一致性。
在创伤性和非创伤性SCI的临床前模型中，在大多数纳入研究中，给予PDE抑制剂似乎与神经行为结果的统计学显著改善相关。然而，证据并不一致，且存在较高的偏倚风险。本综述为解释随后关于PDE抑制剂在脊髓损伤中的临床试验提供了基础。
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150639，标识符：CRD42019150639
