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Updated: Jul 4, 2025
Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin
Published on: August 25, 2022
Cannabidiol reduces intraventricular hemorrhage brain damage, preserving myelination and preventing blood brain
Aarón Del Pozo1, María de Hoz-Rivera1, Angela Romero1
1Biomedical Research Foundation, Hospital Clínico San Carlos - IdISSC, Madrid 28040, Spain.
Insights
Cannabidiol (CBD) shows neuroprotective effects against intraventricular hemorrhage (IVH) in immature rats. CBD treatment reduced brain damage and long-term motor and cognitive deficits, offering a potential therapeutic strategy for IVH.
Area of Science:
- Neuroscience
- Neonatal Research
- Pharmacology
Background:
- Intraventricular hemorrhage (IVH) is a significant cause of disability in preterm infants, lacking effective treatments.
- Immature brain vulnerability to IVH necessitates the exploration of novel therapeutic interventions.
Purpose of the Study:
- To evaluate the neuroprotective potential of cannabidiol (CBD) in a rat model of neonatal intraventricular hemorrhage.
- To assess CBD's effects on brain damage, white matter integrity, and neurobehavioral outcomes following IVH.
Main Methods:
- Neonatal Wistar rats underwent induced IVH, with some receiving prenatal and postnatal CBD treatment.
- Evaluated outcomes included neurobehavioral performance, brain lesion volume, white matter injury markers, blood-brain barrier integrity, inflammation, excitotoxicity, and oxidative stress.
- Histological and biochemical analyses were performed at various time points post-IVH.
Main Results:
- CBD administration significantly ameliorated long-lasting motor and cognitive impairments caused by IVH.
- CBD treatment reduced short- and long-term brain damage, protected oligodendroglial cells, and preserved myelination.
- CBD maintained blood-brain barrier integrity and modulated key pathways involved in inflammation, excitotoxicity, and oxidative stress.
Conclusions:
- Cannabidiol demonstrates robust and pleiotropic neuroprotective effects in immature rats following IVH.
- CBD effectively reduces IVH-induced brain damage and its sequelae, highlighting its potential as a therapeutic agent for neonatal brain injury.
Abstract:
Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. This study assessed the potential neuroprotective effects of cannabidiol (CBD) in an IVH model using immature rats. IVH was induced in 1-day-old (P1) Wistar rats by left periventricular injection of Clostridial collagenase. Some rats received CBD prenatally (10 mg/kg i.p. to the dam) and then 5 mg/kg i.p. 6, 30 and 54 h after IVH (IVH+CBD, n = 30). Other IVH rats received vehicle (IVH+VEH, n = 34) and vehicle-treated non-IVH rats served as controls (SHM, n = 29). Rats were humanely killed at P6, P14 or P45. Brain damage (motor and memory performance, area of damage, Lactate/N-acetylaspartate ratio), white matter injury (ipsilateral hemisphere and corpus callosum volume, oligodendroglial cell density and myelin basic protein signal), blood-brain barrier (BBB) integrity (Mfsd2a, occludin and MMP9 expression, gadolinium leakage), inflammation (TLR4, NFκB and TNFα expression, infiltration of pro-inflammatory cells), excitotoxicity (Glutamate/N-acetylspartate ratio) and oxidative stress (protein nitrosylation) were then evaluated. CBD prevented the long-lasting motor and cognitive consequences of IVH, reduced brain damage in the short- and long-term, protected oligodendroglial cells preserving adequate myelination and maintained BBB integrity. The protective effects of CBD were associated with the modulation of inflammation, excitotoxicity and oxidative stress. In conclusion, in immature rats, CBD reduced IVH-induced brain damage and its short- and long-term consequences, showing robust and pleiotropic neuroprotective effects. CBD is a potential candidate to ameliorate IVH-induced immature brain damage.
