EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA
Background: Hypothermia is standard treatment for neonatal encephalopathy, but near 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms to hypothermia and would improve neuroprotection. Cannabidiol could be a good candidate.Objective: To t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-07-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00323/full |
| _version_ | 1828384458828414976 |
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| author | Hector Lafuente Maria Ruth Pazos Antonia de los Angeles Alvarez Nagat Mohammed Martin Santos Maialen Arizti Francisco Jose Alvarez Jose A Martinez Orgado |
| author_facet | Hector Lafuente Maria Ruth Pazos Antonia de los Angeles Alvarez Nagat Mohammed Martin Santos Maialen Arizti Francisco Jose Alvarez Jose A Martinez Orgado |
| author_sort | Hector Lafuente |
| collection | DOAJ |
| description | Background: Hypothermia is standard treatment for neonatal encephalopathy, but near 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms to hypothermia and would improve neuroprotection. Cannabidiol could be a good candidate.Objective: To test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets.Methods: Hypoxic-ischemic animals were randomized to receive 30 min after the insult: 1) normothermia- and vehicle-treated group; 2) normothermia- and cannabidiol-treated group; 3) hypothermia- and vehicle-treated group; and 4) hypothermia- and cannabidiol-treated group. Six hours after treatment, brains were processed to qualify the number of 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) and expression of caspase-3 (apoptosis) and TNFα (inflammation).Results: Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels. 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 histological damage, was greater than either hypothermia or cannabidiol alone.Conclusion: Cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage. |
| first_indexed | 2024-12-10T05:03:47Z |
| format | Article |
| id | doaj.art-2fb13313b80b4001bb134625f415e64c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-10T05:03:47Z |
| publishDate | 2016-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-2fb13313b80b4001bb134625f415e64c2022-12-22T02:01:19ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-07-011010.3389/fnins.2016.00323190356EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIAHector Lafuente0Maria Ruth Pazos1Antonia de los Angeles Alvarez2Nagat Mohammed3Martin Santos4Maialen Arizti5Francisco Jose Alvarez6Jose A Martinez Orgado7Cruces University HospitalResearch Institute Puerta de HierroUniversity of the Basque CountryResearch Institute Puerta de HierroResearch Institute Puerta de HierroCruces University HospitalCruces University HospitalResearch Institute Puerta de HierroBackground: Hypothermia is standard treatment for neonatal encephalopathy, but near 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms to hypothermia and would improve neuroprotection. Cannabidiol could be a good candidate.Objective: To test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets.Methods: Hypoxic-ischemic animals were randomized to receive 30 min after the insult: 1) normothermia- and vehicle-treated group; 2) normothermia- and cannabidiol-treated group; 3) hypothermia- and vehicle-treated group; and 4) hypothermia- and cannabidiol-treated group. Six hours after treatment, brains were processed to qualify the number of 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) and expression of caspase-3 (apoptosis) and TNFα (inflammation).Results: Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels. 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 histological damage, was greater than either hypothermia or cannabidiol alone.Conclusion: Cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00323/fullCannabidiolHypothermiaNeuroprotectionneurodevelopmentneonatal brainhypoxic-ischemic encephalopathy |
| spellingShingle | Hector Lafuente Maria Ruth Pazos Antonia de los Angeles Alvarez Nagat Mohammed Martin Santos Maialen Arizti Francisco Jose Alvarez Jose A Martinez Orgado EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA Frontiers in Neuroscience Cannabidiol Hypothermia Neuroprotection neurodevelopment neonatal brain hypoxic-ischemic encephalopathy |
| title | EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA |
| title_full | EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA |
| title_fullStr | EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA |
| title_full_unstemmed | EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA |
| title_short | EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA |
| title_sort | effects of cannabidiol plus hypothermia on short term newborn pig brain damage after acute hypoxia ischemia |
| topic | Cannabidiol Hypothermia Neuroprotection neurodevelopment neonatal brain hypoxic-ischemic encephalopathy |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00323/full |
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