Neurotoxicity Research

, Volume 35, Issue 2, pp 463–474 | Cite as

Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats

  • Amanda Nunes Santiago
  • Marco Aurélio Mori
  • Francisco Silveira Guimarães
  • Humberto Milani
  • Rúbia Maria Weffort de OliveiraEmail author


Diabetes and aging are risk factors for cognitive impairments after chronic cerebral hypoperfusion (CCH). Cannabidiol (CBD) is a phytocannabinoid present in the Cannabis sativa plant. It has beneficial effects on both cerebral ischemic diseases and diabetes. We have recently reported that diabetes interacted synergistically with aging to increase neuroinflammation and memory deficits in rats subjected to CCH. The present study investigated whether CBD would alleviate cognitive decline and affect markers of inflammation and neuroplasticity in the hippocampus in middle-aged diabetic rats submitted to CCH. Diabetes was induced in middle-aged rats (14 months old) by intravenous streptozotocin (SZT) administration. Thirty days later, the diabetic animals were subjected to sham or CCH surgeries and treated with CBD (10 mg/kg, once a day) during 30 days. Diabetes exacerbated cognitive deficits induced by CCH in middle-aged rats. Repeated CBD treatment decreased body weight in both sham- and CCH-operated animals. Cannabidiol improved memory performance and reduced hippocampal levels of inflammation markers (inducible nitric oxide synthase, ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and arginase 1). Cannabidiol attenuated the decrease in hippocampal levels of brain-derived neurotrophic factor induced by CCH in diabetic animals, but it did not affect the levels of neuroplasticity markers (growth-associated protein-43 and synaptophysin) in middle-aged diabetic rats. These results suggest that the neuroprotective effects of CBD in middle-aged diabetic rats subjected to CCH are related to a reduction in neuroinflammation. However, they seemed to occur independently of hippocampal neuroplasticity changes.


Brain ischemia Middle-aged rats Diabetes Cannabidiol Neuroprotection 



The authors thank Marco Alberto Trombelli for his technical support. This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), National Institute of Science and Translational Medicine (465458/2014-9), Universidade Estadual de Maringá.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Amanda Nunes Santiago
    • 1
  • Marco Aurélio Mori
    • 1
  • Francisco Silveira Guimarães
    • 2
  • Humberto Milani
    • 1
  • Rúbia Maria Weffort de Oliveira
    • 1
    Email author
  1. 1.Department of Pharmacology and TherapeuticsState University of MaringáMaringáBrazil
  2. 2.Centre for Interdisciplinary Research on Applied Neurosciences (NPNA), Department of Pharmacology, Medical School of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil

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