Background and aim cannabidiol (CBD) leads to significant and long-term sustained neuroprotection in hypoxic-ischaemic (HI) newborn rodents. We aim to determine the temporary therapeutic window (TTW) of CBD. Such TTW is stablished in 6 h for the standard therapy, hypothermia.
Methods 9-day old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, 0.1 mL of vehicle (ethanol:solutol:saline 2:1:17) (HV, n = 25) or CBD (1 mg/kg) was administered s.c. 15 min, or 1, 3, 6, 12 or 24 h after the end of the HI insult (HC0.15 n = 10; HC1, n = 10; HC3, n = 10; HC6, n = 10; HC12, n = 10; HC24, n = 9, respectively). Seven days later MRI scan (T2W) were carried out in formaline-included pup brains (ipsilateral hemisphere volume loss, IVHL), whereas the penumbral peri-lesional area (parieto-occipital cortex) was studied using Nissl staining (necrotic damage, by a neuropathological score, NPS), TUNEL staining (apoptotic damage) and GFAP immunohistochemistry (astrocyte viability). Non-HI mice served as controls (SHM, n = 15).
Results CBD, administered up to 12 h after HI, showed a significant neuroprotective effect, reducing HI-induced IHVL and NPS by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. When CBD administration was delayed 24 h, however, mild neuroprotective effect was still observable regarding NPS or TUNEL, but not IVH loss or astrocyte viability
Conclusions TTW for CBD seems to be between 12 and 24 h after the end of the HI insult.
Supported by FIS PS09/01900, Health Trust South East Norway and GWCRI091190-2.