Potential Treatment Strategies for Ischemic Injuries

The mechanical embolus removal in cerebral ischemia retriever (MERCI retriever) or endovascular mechanical embolectomy is a recently developed 

Ischemic injury is accompanied by the excessive activation of excitatory amino acid receptors, Ca influx, and release of other toxic products that intensify cellular injury (Fig. 3.2). By preventing excitatory neurotransmitter release, neuroprotective agents may reduce deleterious effects of ischemic injury on neural cells. In addition to NMDA receptor channel, Ca + also enters through voltage-gated Ca channels 

Generation of eicosanoids from enzymic metabolism of arachidonic acid initiates inflammatory reactions and the damaged tissue is infiltrated by leukocytes and microglia. The relatively slow pace of these processes, which occur in hours and days that follow an initial stroke, makes them an attractive target for neuroprotective therapy. 

As stated in Chapter 2, the activation of these enzymes causes neuronal death by necrosis and/or apoptosis, via ROS and RNS generation, proteolysis, and DNA damage (Fig. 3.3) (Farooqui et al., 2008). ROS modulate p38/MARK, JNK/MARK, ERK/MARK pathways and RNS activate PARP-1. Under these conditions, in the infarct core neuronal death occurs within minutes to less than an hour (Lo et al., 2003). This is followed by a second wave of neuronal demise in the ischemic penumbra and neuroanatomically connected sites. This delayed cell death (secondary degeneration) occurs via apoptosis and often exceeds the initial damage of 

33 Pathways associated with ROS- and RNS-mediated ceU death in cerebral ischemia. Phosphohpase A2 (PLA2) nitric oxide synthase (NOS) cyclooxygenase-2 (COX-2) arachidonic add (ARA) lyso-phosphophatidylcholine (lyso-PtdCho) platelet-activating factor (RAF) reactive oxygen species (ROS) reactive nitrogen species (RNS) superoxide (O2) peroxynitrite (ONOO ) transcription factor-a (TNF-a) interleukin-ip (IL-ip) and interleukin-6 (IL-6) 

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