Open AccessBAPTA, a calcium chelator, neuroprotects injured neurons in vitro and promotes motor recovery after spinal cord transection in vivo
Author(s) -
Kang Kyuree,
Kim Jin,
Ryu Bokyeong,
Lee SeulGi,
Oh MinSeok,
Baek Jieun,
Ren Xiaoping,
Canavero Sergio,
Kim CYoon,
Chung Hyung Min
Publication year - 2021
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13651
Subject(s) - bapta , spinal cord , spinal cord injury , neuroprotection , medicine , pharmacology , neuroscience , in vivo , calcium , anesthesia , apoptosis , calcium imaging , chemistry , biology , biochemistry , microbiology and biotechnology
Aim Despite animal evidence of a role of calcium in the pathogenesis of spinal cord injury, several studies conducted in the past found calcium blockade ineffective. However, those studies involved oral or parenteral administration of Ca++ antagonists. We hypothesized that Ca++ blockade might be effective with local/immediate application (LIA) at the time of neural injury. Methods In this study, we assessed the effects of LIA of BAPTA (1,2‐bis (o‐aminophenoxy) ethane‐N, N, N′, N'‐tetraacetic acid), a cell‐permeable highly selective Ca++ chelator, after spinal cord transection (SCT) in mice over 4 weeks. Effects of BAPTA were assessed behaviorally and with immunohistochemistry. Concurrently, BAPTA was submitted for the first time to multimodality assessment in an in vitro model of neural damage as a possible spinal neuroprotectant. Results We demonstrate that BAPTA alleviates neuronal apoptosis caused by physical damage by inhibition of neuronal apoptosis and reactive oxygen species (ROS) generation. This translates to enhanced preservation of electrophysiological function and superior behavioral recovery. Conclusion This study shows for the first time that local/immediate application of Ca++ chelator BAPTA is strongly neuroprotective after severe spinal cord injury.