Hypothermia and thiopentone sodium: Individual and combined neuroprotective effects on cortical cultures exposed to prolonged hypoxic episodes

Abstract

Because there are many conflicting reports on cerebroprotective effects of hypothermia and barbiturates, we examined the degree of neuroprotection at defined temperatures (normothermia, 37 degrees C; mild hypothermia, 32 degrees C; deep hypothermia, 22 degrees C; and profound hypothermia, 17 degrees C) and various concentrations (low, 4 microM; moderate, 40 microM; and high, 400 & microM) of thiopentone sodium (TPS), alone and in combination in cortical cultures exposed to prolonged hypoxia (24-48 hr). The survival rate of embryonic day (E)16 Wistar rat cortical neurons was evaluated on photomicrographs before and after experiments. During the 24-hr hypoxic period, the survival rate of neurons was maximal with combinations of mild hypothermia with 40 microM (91.6 +/- 0.7%) and 400 microM TPS (90.8 +/- 0.7%) or deep hypothermia combined with all concentrations of TPS (4 microM, 90.6 +/- 1.0%; 40 microM, 91.4 +/- 0.8%; 400 microM, 91.8 +/- 1.2%). During 48 hr hypoxia, the highest survival rate was seen with the combination of deep hypothermia and either 40 microM (90.9 +/- 0.6%) or 400 microM (91.1 +/- 1.4%) TPS. In the presence of profound hypothermia in combination with all concentrations of TPS, the survival rate was significantly reduced (P< 0.01) compared to combined application of either mild or deep hypothermia with TPS. In summary, maximal neuroprotection was attained with hypothermia and TPS in combination rather than applied individually, during prolonged hypoxic episodes (24- 48 hr). During a 24-hr hypoxic period, both mild and deep hypothermia combined with a clinically relevant concentration of TPS (40 microM) offered the highest neuroprotection. Only deep hypothermia provided maximal neuroprotection when combined with 40 microM TPS, during 48-hr hypoxia. Combination of profound hypothermia and TPS did not confer considerable neuroprotection during long lasting hypoxia.

Moderate hypothermia for 359 operations to clip cerebral aneurysms

“…It might be argued that more aggressive warming would have allowed more patients to be extubated in the operating room and that this might have reduced the incidence of postoperative ventilatory complications. 20…”

Effects of deep hypothermia on nitric oxide‐induced cytotoxicity in primary cultures of cortical neurons

“…The isolation and primary culture of cerebral cortical neurons were carried out as described previously (Shibuta et al,1998,2000,2001; Varathan et al,2001,2002). In brief, the neopallidum free of meninges was removed from Wistar rat (Nihon SLC Hamamatus) fetuses of embryonic day 16, dissected in phosphate‐buffered saline (PBS), treated with 0.25% trypsin at 37°C for 20 min, and triturated with a Pasteur pipette.…”

“…Acute ischemic injury to the brain triggers a cascade of biochemical events that provokes prolonged secondary injury to the surrounding tissues. Hypothermia has been proven to be a potent neuroprotective agent against cerebral ischemia and also has been shown to attenuate neuronal cell death in vitro after hypoxic episodes (Okada et al,1988; Varathan et al,2001,2002). However, the precise mechanisms of neuronal protection by brain hypothermia are largely unknown, and attention has been given mainly to the events occurring during ischemia.…”

Ketamine and thiopental sodium: individual and combined neuroprotective effects on cortical cultures exposed to NMDA or nitric oxide

“…As we reported previously, a high dose of TPS exhibited significant neuroprotection against an NO donor or prolonged hypoxic episode through the free radical scavenging effects of the TPS sulphydryl group (SH). [7][8][9] TPS also decreases both CMR and ICP and inhibits both voltage-gated calcium channels and NMDA receptors. [23][24][25] However, in order to exert this neuroprotective effect, extremely high doses of the barbiturate are necessary, which can elicit undesirable effects, such as circulatory and respiratory depression.…”

“…Consistent with this notion, NMDA blockers, NOS inhibitors and free radical scavengers have been shown to be effective in attenuating NMDA or NO-mediated neurotoxicity. [5][6][7][8][9][10] Ketamine is an i.v. anaesthetic agent that structurally resembles phencyclidine (PCP).…”