Table 2.
Transgenic Studies of Superoxide Dismutase and NADPH Oxidase in Rodent Cerebral Ischemia
| Study | Insult | Main findings |
|---|---|---|
| SOD | ||
| SOD1+/− | pFCI | Decreased cortical infarct (−35%) |
| SOD1+/− | pFCI | No protection |
| SOD1+/− | pFCI | No difference in infarct volume |
| SOD1+/− | TFCI | Decreased infarct |
| SOD1+/− | tFCI | Sustained heat shock protein 70 mRNA expression |
| SOD1+/− | tFCI | Sustained c-fos mRNA expression |
| SOD1+/− | tFCI | Decreased injury (−50%) |
| SOD1+/− | tFCI | Decreased DNA fragmentation |
| SOD1+/− | tFCI | Decreased cytochrome c release |
| SOD1+/− | tFCI | Decreased NF-κB expression |
| SOD1+/− | tFCI | Decreased activation of activator protein-1 |
| SOD1+/− | tFCI | Decreased extracellular signal-regulated kinase activation |
| SOD1+/− | tFCI | Decreased Bad activation |
| SOD1+/− | tFCI | Akt activation |
| SOD1+/− | tFCI | Decreased injury, protein kinase-like endoplasmic reticulum, eIF2α kinase phosphorylation, and glucose-regulated protein 78 release |
| SOD1+/− | tFCI | Increased integrin-linked kinase expression and integrin-linked kinase/Akt complex |
| SOD1+/− | tFCI | Increased murine double minute-2 gene activation; decreased nuclear p53 |
| SOD1+/− | tFCI | Decreased monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α expression |
| SOD1+/− | tFCI | Decreased level of O2−; decreased NF-κB activation and phosphorylation |
| SOD1+/− | tFCI | Increased pPRAS, pPRAS/pAkt binding, and pPRAS/14-3-3 protein binding |
| SOD1+/− | tFCI | Decreased level of O2−; inhibited persistent upregulation of NF-κB |
| SOD1+/− | tFCI | Decreased matrix metalloproteinase activity and Evans blue leakage |
| SOD1+/− | tFCI | Decreased activity of p38, Evans blue leakage, edema, and infarct |
| SOD1+/− | tGCI | Induction of heat shock protein 70 |
| SOD1+/− | tGCI | Decreased injury (−50%) |
| SOD1+/− | tGCI | Decreased injury (−50%) |
| SOD1+/− | tGCI | Decreased active caspase |
| SOD1+/− | tGCI | Decreased endoplasmic reticulum damage |
| SOD1+/− | tGCI | Inhibited apurinic/apyrimidinic endonuclease/redox factor-1 decrease; decreased injury |
| SOD1+/− | tGCI | Increased pAkt and p-glycogen synthase kinase-3β expression |
| SOD1+/− | tGCI | Decreased p53 translocation to mitochondria |
| SOD1+/− | tGCI | Decreased p53-upregulated modulator of apoptosis activation and injury |
| SOD1−/− | pFCI | No difference in infarct volume |
| SOD1−/− | tFCI | Increased infarct, swelling, and mortality |
| SOD1−/− | tFCI | Increased lesion size and edema |
| SOD1−/− | tGCI | Increased cell death |
| SOD1−/− | tFCI | Increased blood–brain barrier disruption |
| SOD2+/− | tFCI | Decreased brain injury |
| SOD2−/+ | tFCI Hyperglycemia | Increased brain infarction |
| SOD2−/+ | pFCI | Increased infarct (66%) |
| SOD2−/+ | pFCI | Cytochrome c release and DNA fragmentation increase |
| SOD2−/+ | tFCI | Increased cytochrome c release |
| SOD2−/+ | tFCI | Increased brain infarction, neurological deficits |
| SOD2−/+ | tFCI | Increased blood–brain barrier damage |
| SOD2−/+ | tFCI | Increased infarction, hemorrhage |
| NADPH oxidase | ||
| Gp91phox−/− | tFCI | Reduced infarct (72) |
| Gp91phox−/− | tFCI | Reduced infarct (13) |
| p47phox−/− | HG/GR | Reduced neurodegeneration and mortality (69) |
| p47phox−/− | Forebrain I/R | Reduced neurodegeneration and mortality (70) |
All data from References 9 and 53, unless otherwise noted.
NF-κB, nuclear factor kappa B; pFCI, permanent focal cerebral ischemia; pPRAS, phosphorylated proline-rich Akt substrate; tFCI, transient FCI; tGCI, transient global cerebral ischemia.