Perinatal neuroprotection by muscle relaxants against hypoxic-ischemic lesions: is it a possible hypothesis?
The incidence of neurological disabilities ascribable to hypoxia-ischemia in the perinatal period (HIPP) is rising. Glutamate plays a key role in the development of cerebral damage related to HIPP: it triggers the excitotoxic cascade by overactivating N-methyl-D-aspartate receptors (NMDA), implicated as important mediators of both learning and neuronal development. Laudanosine is the metabolite of the neuromuscular blocking drugs, atracurium and cisatracurium, administered as part of obstetric general anesthesia. In elective cesarean section, laudanosine may be found in the fetus with a mean umbilical vein concentration of 26 (range 6-60) ng ml(-1). At nM concentrations, laudanosine can activate alpha4beta2 nACh subtype receptors. Activation of alpha4beta2 nAChRs provided neuroprotection against NMDA excitotoxic cascade in a neonatal model. Taken together, experimental and clinical data widely indicate a potential neuroprotective role for laudanosine against perinatal brain lesions of hypoxic-ischemic origin. The clinical relevance is that administration of the neuromuscular blocking drugs atracurium and cisatracurium, administered as part of general anesthesia for cesarean section, could be potentially therapeutic in obstetric anesthesia. Therefore, we find laudanosine to be an attractive proposal for further studies in the prevention of neurological disabilities ascribable to perinatal injury related to hypoxia and ischemia.