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Neuroprotective effects of clavulanic acid following permanent bilateral common carotid artery occlusion in rats
Author(s) -
Ghanbarabadi Mustafa,
Falanji Farahnaz,
Rad Abolfazl,
Chazani Sharahi Nafiseh,
Amoueian Sakineh,
Amin Mohamadreza,
Molavi Mehdi,
Amin Bahareh
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21595
Subject(s) - morris water navigation task , neocortex , clavulanic acid , hippocampus , neuroprotection , common carotid artery , medicine , vascular dementia , anesthesia , endocrinology , pharmacology , pathology , biology , dementia , carotid arteries , biochemistry , disease , amoxicillin , psychiatry , antibiotics
We investigated whether clavulanic acid could improve learning and memory, in rats underwent bilateral occlusion of common carotid artery (2VO). Seventy male Wistar rats were subjected to 2VO, with a 1‐week interval between right and left artery occlusions. After 2VO, animals received clavulanic acid (10, 20, 40 mg/kg, intraperitoneally), from day 8 to 20. Spatial memory was assessed in the Morris water maze, 1 week after the induction of 2VO (day 15). The mRNA expression levels of bcl‐2, bcl2‐associated x protein (bax), caspase‐3, inducible nitric oxide synthase (iNOS), and amyloid beta precursor protein (APP) were measured in the neocortex and hippocampus. Clavulanic acid significantly decreased the escape latency and swimming time in the training trial days. As well, it increased time and distance percentage in the target quadrant, while it decreased such factors in the opposite quadrant in the final trial day, compared to 2VO + normal saline animals. Real time‐PCR data showed a significant higher mRNA expression of bax, caspase 3, and iNOS in the hippocampus and neocortex of 2VO animal compared to nonoccluded rats. APP increased in the neocortex but not hippocampus. Compared with 2VO animals, clavulanic acid significantly down‐regulated the expression of iNOS, caspase 3, and APP, accompanied by diminishing the bax/bcl2 ratio. Our results reveal a potential therapeutic use of clavulanic acid for cognitive dysfunction associated with cerebral hypoperfusion in vascular dementia and Alzheimer disease.