Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury

• Published in: International journal of molecular sciences 2020-11, Vol.21 (21), p.8256
• Main Authors: Park, Min Kyu, Choi, Bo Young, Kho, A Ra, Lee, Song Hee, Hong, Dae Ki, Jeong, Jeong Hyun, Kang, Dong Hyeon, Kang, Beom Seok, Suh, Sang Won
• Format: Article
• Language: English
• Subjects: Animals; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Brain Injuries, Traumatic - physiopathology; Cell Count; Cell Death - drug effects; Disease Models, Animal; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Male; neuronal death; Neurons - drug effects; Neurons - pathology; Neurons - physiology; Nitroso Compounds - pharmacology; Nitroso Compounds - therapeutic use; NU6027; Oxidative Stress - drug effects; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Rats; Rats, Sprague-Dawley; transient receptor potential cation channel 5; traumatic brain injury; TRPC Cation Channels - antagonists & inhibitors; zinc; Zinc - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21218256

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.