ArticleFrontiers in neuroscience2016
Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia.
Article in Frontiers in neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.Molecular neurobiology · 2025Pooled it
- Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- Epilepsy, neuroinflammation and cannabidiol What do we know thus far?Frontiers in pharmacology · 2025Review
- Cannabidiol effectively prevents oxidative stress and stabilizes hypoxia-inducible factor-1 alpha (HIF-1α) in an animal model of global hypoxia.Scientific reports · 2024Article
- Potential of CBD Acting on Cannabinoid Receptors CBInternational journal of molecular sciences · 2024Review
- Research progress in the management of vascular disease with cannabidiol: a review.Journal of cardiothoracic surgery · 2024Review
- Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine AInternational journal of molecular sciences · 2023Article
- Protein Carbonylation as a Biomarker of Oxidative Stress and a Therapeutic Target in Neonatal Brain Damage.Antioxidants (Basel, Switzerland) · 2023Review
- Neuroprotective Efficacy of Betulinic Acid Hydroxamate, a B55α/PP2A Activator, in Acute Hypoxia-Ischemia-Induced Brain Damage in Newborn Rats.Translational stroke research · 2023Article
- Neuroprotective therapies in the NICU in term infants: present and future.Pediatric research · 2023Review
- Effects of Cannabidiol, Hypothermia, and Their Combination in Newborn Rats with Hypoxic-Ischemic Encephalopathy.eNeuro · 2023Article
- Role of integrating cannabinoids and the endocannabinoid system in neonatal hypoxic-ischaemic encephalopathy.Frontiers in molecular neuroscience · 2023Review
- No neuroprotective effect of therapeutic hypothermia following lipopolysaccharide-sensitized hypoxia-ischemia: a newborn piglet study.Frontiers in pediatrics · 2023Article
- Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage.Frontiers in pharmacology · 2023Review
- The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury.Biomedicines · 2022Review
- New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy.European journal of pediatrics · 2022Review
- Cannabinoids as Glial Cell Modulators in Ischemic Stroke: Implications for Neuroprotection.Frontiers in pharmacology · 2022Review
- Hypothermia modulates myeloid cell polarization in neonatal hypoxic-ischemic brain injury.Journal of neuroinflammation · 2021Article
- Effects of Hypothermia and Allopurinol on Oxidative Status in a Rat Model of Hypoxic Ischemic Encephalopathy.Antioxidants (Basel, Switzerland) · 2021Article
- Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult.
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Registered trials
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