The endocannabinoid system plays a role in neonatal Hypoxic-ischemic encephalopathy. cannabinoid receptors CB1 and CB2 are upregulated and endocannabinoids like AEA, 2-AG, OEA and PEA show increased levels after cerebral ischemia (England et al., 2015; Lara-Celador et al., 2013).
These increased levels of endocannabinoids would reduce apoptotic cell death and reduce brain injury (Lara-Celador et al., 2012).
The endocannabinoid system would be involved in the reduction of glutamate excitotoxicity, neuroinflammation and oxidative stress (Booz, 2011; Capettini et al., 2012; Fernández-López et al., 2013)
Selective activation of CB1 reduces astrocytic reaction, neuronal death and dendritic loss in a stoke model in adult mice (Caltana et al., 2015).
Selective activation of CB2 reduces neuroinflammation, ischemic injury and cognitive deficits in different models of stroke, probably through modulation of AMPK/CREB signaling (Choi et al., 2013; Ronca et al., 2015; Zarruk et al., 2012).
Selective stimulation of CB2 (SR-144528) significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia (Li et al., 2015).
Activation of CB1 and CB2 through synthetic cannabinoid WIN 55,212-2 in different hypoxia-ischemic newborn animal models showed neuroprotective effects, decreased brain injury and reduced apoptotic cell death by acting on glutamatergic excitotoxicity, TNF-alpha release, and iNOS expression (Alonso-AlcoNADA et al., 2010, 2012, Fernández-López et al., 2006, 2007, 2010; Martínez-Orgado et al., 2003).
Activation of PPAR-γ receptor showed behavioral recovery and microglial supression in a model of stroke (Yu et al., 2015).
CBD showed neuroprotective effects with functional and behavioral recovery in hypoxia-ischemic animal models (Alvarez et al., 2008; Lafuente et al., 2011).
CBD increased neuronal and astrocyte survival and reduced brain damage and reactive astrogliosis (Hayakawa et al., 2009; Schiavon et al., 2014).
CBD mechanisms would involve the modulation of excitotoxicity, oxidatice stress and inflammation through CB2, 5HT1A, A(2A) and PPAR-γ receptors (Castillo et al., 2010; Hind et al., 2015; Pazos et al., 2012, 2013) .
For more information about cannabinoids in hypoxia-ischemic brain injury and stroke see Alonso-AlcoNADA (2011) and Fernández-Ruiz (2015).
References:
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