TBI-Mediated Alterations in Enzymic Activities

Glutamate-mediated calcium influx results in stimulation arachidonic acid release from neural membrane glycerophospholipids. This release is catalyzed by CPLA2 and PLC/DAG-lipase pathway (McIntosh et al., 1998 Schuhmann et al., 2003 Shohami et al., 1987, 1989 Wei et al., 1982 Dhillon et al., 1996 Homayoun et al., 1997, 2000). Arachidonic acid release occurs in traumatic as well as fluid percussion models of brain injury (FPI). Enzymic oxidation of arachidonic acid generates prostaglandins, leukotrienes, and thromoboxanes whereas non-enzymic oxidation produces isoprostanes and ROS which include superoxide and hydroxyl radicals (Farooqui and Horrocks, 2007). 

Astroglial response to TBI is characterized by hyperplasia and upregulation in glial fibrillary acidic protein (Table 6.2). The reactive astrocytes also express neurotrophic factors, and cytokines, which modulate the generation of recognition molecules allowing the support of post-lesional axonal regrowth. Major 

Free fatty acid levels Increased Philhs et al. (2006) 

Oxidative stress intensity Increased Farooqui and Horrocks (2009) 

COX-2 is an important mediator of neuroinflammation (Phillis et al., 2006). PGE2 has been implicated in neuroinflammation and the apoptosis of cortical cells through the activation of the EP2 reeeptor, which in turn activates caspase-3, a pro-apoptotic agent (Takadera et al., 2002). Concussive injury of the rat cerebral cortex causes a bilateral induction of COX-2 mRNA in the cortex and dentate gyrus. COX-2 activity is detectable in these areas and persisted in the ipsilateral cortex for at least 72 h (Kunz et al., 2002). Furthermore, a persistent accumulation of microglial cells and macrophages expressing COX-1 is also observed in human 

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