Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets

Francisco J. Alvarez, Hector Lafuente, M. Carmen Rey-Santano, Victoria E. Mielgo, Elena Gastiasoro, Miguel Rueda, Roger G. Pertwee, Ana I. Castillo, Julian Romero, Jose Martinez-Orgado

Research output: Contribution to journalArticle

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Abstract

To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia). Nonhypoxic-ischemic sham-operated piglets remained as controls. Brain damage was studied by near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) and by histologic assessment (Nissl and FluoroJadeB staining). In HI+vehicle, HI led to severe cerebral hemodynamic and metabolic impairment, as reflected in NIBS by an increase in total Hb index (THI) and a decrease in the fractional tissue oxygenation extraction (FTOE); in HI+CBD the increase of THI was blunted and FTOE remained similar to SHAM. HI profoundly decreased EEG amplitude, which was not recovered in HI+vehicle, indicating cerebral hypofunction; seizures were observed in all HI+vehicle. In HI+CBD, however, EEG amplitude recovered to 46.4 +/- 7.8% baseline and seizures appeared only in 4/8 piglets (both p < 0.05). The number of viable neurons decreased and that of degenerating neurons increased in HI+vehicle; CBD reduced both effects by more than 50%. CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects. In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits. (Pediatr Res 64: 653-658, 2008)

Original languageEnglish
Pages (from-to)653-658
Number of pages6
JournalPediatric Research
Volume64
Issue number6
DOIs
Publication statusPublished - Dec 2008

Keywords

  • near-infrared spectroscopy
  • cerebral hemodynamics
  • reperfusion injury
  • brain activity
  • oxygenation
  • model
  • rats
  • encephalopathy
  • damage
  • birth

Cite this

Alvarez, F. J., Lafuente, H., Rey-Santano, M. C., Mielgo, V. E., Gastiasoro, E., Rueda, M., ... Martinez-Orgado, J. (2008). Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets. Pediatric Research, 64(6), 653-658. https://doi.org/10.1203/PDR.0b013e318186e5dd

Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets. / Alvarez, Francisco J.; Lafuente, Hector; Rey-Santano, M. Carmen; Mielgo, Victoria E.; Gastiasoro, Elena; Rueda, Miguel; Pertwee, Roger G.; Castillo, Ana I.; Romero, Julian; Martinez-Orgado, Jose.

In: Pediatric Research, Vol. 64, No. 6, 12.2008, p. 653-658.

Research output: Contribution to journalArticle

Alvarez, FJ, Lafuente, H, Rey-Santano, MC, Mielgo, VE, Gastiasoro, E, Rueda, M, Pertwee, RG, Castillo, AI, Romero, J & Martinez-Orgado, J 2008, 'Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets', Pediatric Research, vol. 64, no. 6, pp. 653-658. https://doi.org/10.1203/PDR.0b013e318186e5dd
Alvarez, Francisco J. ; Lafuente, Hector ; Rey-Santano, M. Carmen ; Mielgo, Victoria E. ; Gastiasoro, Elena ; Rueda, Miguel ; Pertwee, Roger G. ; Castillo, Ana I. ; Romero, Julian ; Martinez-Orgado, Jose. / Neuroprotective Effects of the Nonpsychoactive Cannabinoid Cannabidiol in Hypoxic-Ischemic Newborn Piglets. In: Pediatric Research. 2008 ; Vol. 64, No. 6. pp. 653-658.
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AU - Lafuente, Hector

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AU - Mielgo, Victoria E.

AU - Gastiasoro, Elena

AU - Rueda, Miguel

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N2 - To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia). Nonhypoxic-ischemic sham-operated piglets remained as controls. Brain damage was studied by near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) and by histologic assessment (Nissl and FluoroJadeB staining). In HI+vehicle, HI led to severe cerebral hemodynamic and metabolic impairment, as reflected in NIBS by an increase in total Hb index (THI) and a decrease in the fractional tissue oxygenation extraction (FTOE); in HI+CBD the increase of THI was blunted and FTOE remained similar to SHAM. HI profoundly decreased EEG amplitude, which was not recovered in HI+vehicle, indicating cerebral hypofunction; seizures were observed in all HI+vehicle. In HI+CBD, however, EEG amplitude recovered to 46.4 +/- 7.8% baseline and seizures appeared only in 4/8 piglets (both p < 0.05). The number of viable neurons decreased and that of degenerating neurons increased in HI+vehicle; CBD reduced both effects by more than 50%. CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects. In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits. (Pediatr Res 64: 653-658, 2008)

AB - To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia). Nonhypoxic-ischemic sham-operated piglets remained as controls. Brain damage was studied by near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) and by histologic assessment (Nissl and FluoroJadeB staining). In HI+vehicle, HI led to severe cerebral hemodynamic and metabolic impairment, as reflected in NIBS by an increase in total Hb index (THI) and a decrease in the fractional tissue oxygenation extraction (FTOE); in HI+CBD the increase of THI was blunted and FTOE remained similar to SHAM. HI profoundly decreased EEG amplitude, which was not recovered in HI+vehicle, indicating cerebral hypofunction; seizures were observed in all HI+vehicle. In HI+CBD, however, EEG amplitude recovered to 46.4 +/- 7.8% baseline and seizures appeared only in 4/8 piglets (both p < 0.05). The number of viable neurons decreased and that of degenerating neurons increased in HI+vehicle; CBD reduced both effects by more than 50%. CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects. In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits. (Pediatr Res 64: 653-658, 2008)

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KW - damage

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