Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol’s ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol’s role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol’s promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.

Cannabidiol reduces intraventricular hemorrhage brain damage, preserving myelination and preventing blood brain barrier dysfunction in immature rats

“…administered to the dam 24 ​h before delivery produced a concentration (0.03 ​± ​0.004 ​ng/mg) in pup brains at birth previously shown to be neuroprotective in hypoxic-ischemic neonatal rats [ 16 ]. Post-insult dose of CBD (5 ​mg/kg) was selected after previous experiments by our group showing robust neuroprotective effects of that dose in neonatal rats exposed to hypoxic-ischemic insults [ 11 , 16 ]. Different dosage regimes were tested: Single administration of 10 ​mg/kg i.p.…”

“…A set of sensorimotor and cognitive tests were performed at P14 or P45, as detailed elsewhere [ 11 , 15 , 16 ]. All tests were video recorded to be assessed by three different examiners blinded to the experimental group.…”

“…To assess long-term effects on myelination, immunohistochemistry studies were performed at P45 by a researcher blinded to the experimental group as previously reported [ 11 , 15 , 16 ]. Paraffin embedded coronal sections (4 ​μm thick) were obtained at a level corresponding to plate 21 of the Paxino's atlas [ 17 ].…”

“…Paraffin embedded coronal sections (4 ​μm thick) were obtained at a level corresponding to plate 21 of the Paxino's atlas [ 17 ]. Studies were performed on the external capsule at that level because this has demonstrated to be the optimal area to assess myelination in the immature brain [ 11 ]. Tissue was incubated overnight at room temperature with Myelin Basic Protein (MBP) antibodies (1:600; Merck KGaA, Darmstadt, Germany).…”

“…The antioxidant properties of CBD have recently increased the interest in this compound as a treatment for brain damage after intracerebral hemorrhage [ 10 ]. Furthermore, the neuroprotective effects of CBD in hypoxic-ischemic newborn rats leads to the prevention of WMI [ 11 ].…”