Endocannabinoids and TBI

Endocannabinoids include arachidonylethanolamine, noladin, arachidonyldopa-mine, 2-arachidonylglycerol (2-AG), and arachidonylethanolamide (anandamide) (Fig. 7.8). 2-AG and anandamide are derived from the non-oxidative metabolism of arachidonic acid (ARA). 2-AG and anandamide are synthesized through 

1- lyso-2-arachidonyl-PtdCho and A-arachidonyl-PtdEtn. This reaction is catalyzed by a Ca -dependent, membrane-associated A-acyltransferase. 1-Lyso-arachidonyl-PtdCho is converted to 2-AG by PEC and A-arachidonyl-PtdEtn is transformed into anandamide by A-acylphosphatidylethanolamine-specific PLD (NAPE-PLD), a member of the metallo- -lactamase family, which specifically hydrolyzes N-acylphosphatidylethanolamine among glycerophospholipids, and appears to be constitutively active (Di Marzo et al., 1996 Ueda et al., 2005) (Eig. 7.9). An alternative pathway for the synthesis of 2-AG involves the hydrolysis of 1,2-arachidonyl-PtdCho by PEG, followed by the action of DAG-lipase on 1-acyl- 

2- arachidonylglycerol. Two types of cannabinoid receptor (CBi and CB2) have been reported to occur in mammalian tissues. The CBi receptors are abundantly expressed in the brain, whereas CB2 receptors are limited to lymphoid organs. 2-AG and anandamide nonselectively bind to both CBi and CB2 receptors and act as neurotransmitter or neuromodulators in the brain, immune, and cardiovascular systems. Endocannabinoids modulate brain function through cannabinoid 

7 Potential Neuroprotective Strategies for Traumatic Brain Injury 

---