Genetic vulnerability of cortical neurons isolated from stroke-prone spontaneously hypertensive rats in hypoxia and oxygen reperfusion

Severe hypertension and cerebrovascular diseases develop in stroke-prone sp ontaneously hypertensive rats (SHRSP), Cortical neurons from SHRSP are more vulnerable than those from Wistar Kyoto rats (WKY) to the effects of nitri c oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. G rowth factors, idebenone, and nilvadipine (a Ca2+ channel blocker) can redu ce neuronal damage caused by hypoxia or neurotoxic agents. This study was d esigned to determine 1) whether cortical neurons from SHRSP are more vulner able than those from WKY and 2) whether neuronal damage is minimized by the so-called neuroprotective agents in cells exposed to hypoxia and oxygen re perfusion. We demonstrated that 6 to 24 h of hypoxia did not increase cell death in either WKY or SHRSP, whereas 36 h of hypoxia significantly increas ed cell death in SHRSP (p < 0.01). Furthermore, 6 to 36 h of hypoxia and 1. 5 to 5 h of reperfusion heavily damaged cells from both strains of rats, an d most cells became apoptotic or necrotic, We also verified that the abilit y to protect neurons in hypoxia and oxygen reperfusion was as follows: ideb enone > insulin-like growth factor-1 (IGF-1) > nilvadipine. These data indi cate that oxygen radical generation occurs and the free radicals heavily da mage neurons in hypoxia and oxygen reperfusion, SHRSP neurons are weaker th an WKY neurons in these conditions, Furthermore, we surmise that idebenone, an antioxidant, decreases free radicals, and IGF-1 attenuates p(53)-mediat ed apoptosis and thereby prevents cell death, We conclude that antioxidants are more potent than IGF-1 in protecting cortical neurons from damage caus ed by hypoxia and oxygen reperfusion, although both are very useful in mini mizing damage to cortical neurons.