Abstract
Background: Exogenous and endogenous cannabinoids [CBs] exert neuroprotective and anti inflammatory actions on glia and neurons. Two CB receptors have been identified. Evidence supports cannabinoid receptor- and non receptor-mediated modes of action in blocking NMDA signaling and the inhibition of free radicals and TNF alpha secretion.
Objective: The present study was designed to assess the neuroprotective effects of endogenous cannabinoid Anandamide using in vivo well-defined mouse model of neonatal excitotoxic brain lesions, which mimic several aspects of brain damage associated with human cerebral palsy.
Methods: Mouse pups [postnatal age 5] were injected intrapallially with ibotenate acting on NMDA and metabotropic receptors, or S-bromowillardiine acting on AMPA-kainate receptors to produce excitotoxic stress and brain lesions immediately followed by intraperitoneal injection of Anandamide injected also 4, 8 and 12 hours later in the S-bromowillardiine injected pups. CB-1 receptor agonist [ACPA] was immediately injected intraperitoneally in the S-bromowillardiine injected pups. A CB-1 receptor antagonist [AM251] and a CB-2 receptor antagonist [AM630] were injected in S-bromowillardiine immediately Anandamide injected pups. Pups were sacrificed 5 days after the excitotoxic challenge.
Results: Anandamide slightly protected the cortex but had no significant effect on white matter in ibotenate-induced excitotoxic stress. In S-bromowillardiine pups, Anadamide provided dose-dependent neuroprotective effect on both cortex and white matter. This effect was mimicked by a ACPA and was blocked by a CB-1 receptor antagonist [AM251] but not CB-2 receptor antagonist [AM630]. Neuroprotection is observed when Anandamide was injected immediately or 4 hours after S-bromowillardiine but not 8 or 12 hours after the insult with a long-lasting effect as it was still observed when pups were sacrificed 25 days after the insult.
Conclusion: Findings indicate that cannabinoids provide some neuroprotection in these models through CB-1 receptor mediated mode of action in blocking NMDA signaling.
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Shouman, B., Schwendimann, L. & Gressens, P. 347 Cannabinoids Protect Against Excitotoxic Brain Lesions in Newborn Mice. Pediatr Res 58, 414 (2005). https://doi.org/10.1203/00006450-200508000-00376
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DOI: https://doi.org/10.1203/00006450-200508000-00376