Abstract
Background: A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage.
Objective: To test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage.
Method: 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1 mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after the end of the HI insult. Seven days later brain damage was assessed using T2W Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and histological studies: Nissl staining (neuropathological score), TUNEL staining (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein (astrocyte viability) or ionized calcium binding adaptor molecule (microglial activation).
Results: CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction.
Conclusion: CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia.
Keywords: Cannabidiol, hypoxia-ischemia, newborn, mice, therapeutic window.
CNS & Neurological Disorders - Drug Targets
Title:Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice
Volume: 16 Issue: 1
Author(s): Nagat Mohammed, Maria Ceprian, Laura Jimenez, M. Ruth Pazos and Jose Martínez-Orgado
Affiliation:
Keywords: Cannabidiol, hypoxia-ischemia, newborn, mice, therapeutic window.
Abstract: Background: A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage.
Objective: To test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage.
Method: 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1 mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after the end of the HI insult. Seven days later brain damage was assessed using T2W Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and histological studies: Nissl staining (neuropathological score), TUNEL staining (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein (astrocyte viability) or ionized calcium binding adaptor molecule (microglial activation).
Results: CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction.
Conclusion: CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia.
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Cite this article as:
Mohammed Nagat, Ceprian Maria, Jimenez Laura, Pazos Ruth M. and Martínez-Orgado Jose, Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice, CNS & Neurological Disorders - Drug Targets 2017; 16 (1) . https://dx.doi.org/10.2174/1871527315666160927110305
DOI https://dx.doi.org/10.2174/1871527315666160927110305 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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