Kidd Benjamin M, Varholick Justin A, Tuyn Dana M, Kamat Pradip K, Simon Zachary D, Liu Lei, Mekler Mackenzie P, Pompilus Marjory, Bubenik Jodi L, Davenport Mackenzie L, Carter Helmut A, Grudny Matteo M, Barbazuk W Brad, Doré Sylvain, Febo Marcelo, Candelario-Jalil Eduardo, Maden Malcolm, Swanson Maurice S
Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.
Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
NPJ Regen Med. 2024 Dec 20;9(1):41. doi: 10.1038/s41536-024-00386-8.
Stroke is a major cause of disability for adults over 40 years of age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to a severe stroke injury in a highly regenerative adult mammal. Here we investigate the effects of transient ischemia on adult spiny mice, Acomys cahirinus, due to their ability to regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and Acomys showed rapid behavioral recovery post-stroke yet failed to regenerate impacted brain regions. An Acomys brain atlas in combination with functional (f)MRI demonstrated recovery coincides with neuroplasticity. The strength and quality of the global connectome are preserved post-injury with distinct contralateral and ipsilateral brain regions compensating for lost tissue. Thus, we propose Acomys recovers functionally from an ischemic stroke injury not by tissue regeneration but by altering its brain connectome.
中风是40岁以上成年人残疾的主要原因。虽然对动物模型的研究优先考虑旨在减少中风后损伤的治疗方法,但尚无研究调查高度再生的成年哺乳动物对严重中风损伤的反应。在此,我们研究短暂性缺血对成年多刺小鼠(埃及刺毛鼠)的影响,因为它们能够再生多种组织且不留疤痕。我们进行了短暂性大脑中动脉闭塞手术,结果显示多刺小鼠在中风后行为恢复迅速,但受影响的脑区未能再生。结合功能磁共振成像(fMRI)的多刺小鼠脑图谱表明,恢复与神经可塑性相吻合。损伤后,整体脑连接组的强度和质量得以保留,对侧和同侧不同的脑区补偿了丢失的组织。因此,我们认为多刺小鼠从缺血性中风损伤中功能恢复并非通过组织再生,而是通过改变其脑连接组来实现。